Production of fatty olefin derivatives via olefin metathesis

ABSTRACT

In one aspect, the invention provides a method for synthesizing a fatty olefin derivative. The method includes: a) contacting an olefin according to Formula Iwith a metathesis reaction partner according to Formula IIbin the presence of a metathesis catalyst under conditions sufficient to form a metathesis product according to Formula IIIb:andb) converting the metathesis product to the fatty olefin derivative. Each R1 is independently selected from H, C1-18 alkyl, and C2-18 alkenyl; R2b is C1-8 alkyl; subscript y is an integer ranging from 0 to 17; and subscript z is an integer ranging from 0 to 17. In certain embodiments, the metathesis catalyst is a tungsten catalyst or a molybdenum catalyst. In various embodiments, the fatty olefin derivative is a pheromone. Pheromone compositions and methods of using them are also described.

CROSS-REFERENCES TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 15/721,018, filed on Sep. 29, 2017 and issued as U.S. Pat. No.10,596,562, which is a continuation of U.S. patent application Ser. No.15/354,916, filed on Nov. 17, 2016 and issued as U.S. Pat. No. 9,776,179on Oct. 3, 2017, which claims priority to U.S. Provisional Pat. Appl.No. 62/257,148, filed on Nov. 18, 2015, which applications areincorporated herein by reference in their entirety.

BACKGROUND OF THE INVENTION

Insect infestation is a primary cause of crop loss throughout the UnitedStates. A wide variety of chemical pesticides has been relied upon inthe past to control insect pests. However, environmental concerns aswell as consumer safety concerns have led to the de-registration of manypesticides and a reluctance to use others on agricultural products whichare ultimately consumed as food. As a consequence, there is a desire forthe development of alternative biological control agents.

Pheromones are chemicals which are secreted outside the body of insectscan be classified according to the type of behavioral reaction theyinduce. Pheromone classes include aggregation pheromones, sexualpheromones, trail pheromones, and alarm pheromones. Sex pheromones, forexample, are typically secreted by insects to attract partners formating.

When pheromones are dispersed on leaves of a crop plant, or in anorchard environment in small quantities over a continuous period oftime, pheromone levels reach thresholds that can modify insect behavior.Maintenance of pheromone levels at or above such thresholds can impactinsect reproductive processes and reduce mating. Use of pheromones inconjunction with conventional insecticides can therefore reduce thequantity of insecticide required for effective control and canspecifically target pest insects while preserving beneficial insectpopulations. These advantages can reduce risks to humans and theenvironment and lower overall insect control costs.

Despite these advantages, pheromones are not widely used today becauseof the high cost of active ingredient (AI). Even though thousands ofinsect pheromones have been identified, less than about twenty insectpests worldwide are currently controlled using pheromone strategies, andonly 0.05% of global agricultural land employs pheromones. Lepidopteranpheromones, which are naturally occurring compounds, or identical orsubstantially similar synthetic compounds, are designated by anunbranched aliphatic chain (between 9 and 18 carbons) ending in analcohol, aldehyde, or acetate functional group and containing up to 3double bonds in the aliphatic backbone. Improved methods for preparinglepidopteran insect pheromones and structurally related compounds areneeded. The present invention meets this and other needs.

BRIEF SUMMARY OF THE INVENTION

In a first aspect, the invention provides a method for synthesizing afatty olefin derivative. The method includes:

-   -   a) contacting an olefin according to Formula I

-   -   with a metathesis reaction partner according to Formula II

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form a metathesis product; and    -   b) optionally converting the metathesis product to the fatty        olefin derivative;    -   wherein:    -   R¹ is selected from H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl;    -   R² is selected from —(CH₂)_(x) OR^(2a) and —(CH₂)_(y)COOR^(2b),        wherein R^(2a) is an alcohol protecting group and R^(2b) is C₁₋₈        alkyl;    -   subscript x is an integer ranging from 1 to 18;    -   subscript y is an integer ranging from 0 to 17; and    -   subscript z is an integer ranging from 0 to 17.

In some embodiments, the metathesis catalyst is a tungsten metathesiscatalyst, a molybdenum metathesis catalyst, or a ruthenium metathesiscatalyst. In certain embodiments, the metathesis catalyst is a tungstencatalyst or a molybdenum catalyst.

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIa:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and wherein the metathesis product is a compound according to        Formula IIIa:

In some embodiments, converting the metathesis product to the fattyolefin derivative includes removing R^(2a) from the compound of FormulaIIIa to form an alkenol according to Formula Va:

In some embodiments, the alkenol of Formula Va is the pheromone. In someembodiments, converting the metathesis product to the fatty olefinderivative further includes acylating the alkenol of Formula Va, therebyforming a fatty olefin derivative according to Formula VIa:

wherein R^(2c) is C₁₋₆ acyl.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes oxidizing the alkenol of Formula Va,thereby forming a fatty olefin derivative according to Formula VIIa:

In some embodiments, the metathesis reaction partner is an esteraccording to Formula IIb:

-   -   and subscript z is an integer ranging from 1 to 18; and    -   wherein the metathesis product is a compound according to        Formula IIIb:

In some embodiments, converting the metathesis product to the fattyolefin derivative includes reducing the metathesis product of FormulaIIIb to form an alkenol according to Formula Vb:

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIa or Formula IIb and the metathesisproduct is a compound according to Formula IV:

In some embodiments, R¹ in the compound of Formula IV is C₂₋₁₈ alkenyl.

A number of pheromones and pheromone precursors, including unsaturatedfatty alcohols, unsaturated fatty alcohol acetates, unsaturated fattyaldehydes, unsaturated fatty acid esters, and polyenes, can besynthesized using the methods of the invention.

DETAILED DESCRIPTION OF THE INVENTION I. Introduction

The present invention provides methods for the synthesis of fatty olefinderivatives (such as straight-chain lepidopteran pheromones; SCLPs)through the cross-metathesis of protected fatty alcohols or fatty acidesters with olefins (e.g., α-olefins). Through the use of a variety offatty alcohols, fatty acid alkyl esters and α-olefin feedstocks inconcert with olefin metathesis catalysts (including Group VI Z-selectivecatalysts), a wide variety of protected unsaturated fatty alcoholprecursors with high Z-olefin content can be obtained. These precursorcompounds can be converted to pheromones (e.g., long chain Z-alcohols,Z-aldehydes, Z-acetates, and Z-nitrates) and other useful fatty olefinderivatives as described in detail below. Alternatively, non-selectiveolefin metathesis catalysts (including Group VI non-selective catalysts)can be used to generate cis/trans mixtures of protected long chain fattyalcohols. Such mixtures can be refined to provide pure E-pheromoneprecursors and other fatty E-olefin derivatives via Z-selectiveethenolysis. The methods provide access to valuable products, includingSCLPs containing 7-, 9-, or 10-monounsaturation.

II. Definitions

The following definitions and abbreviations are to be used for theinterpretation of the invention. The term “invention” or “presentinvention” as used herein is a non-limiting term and is not intended torefer to any single embodiment but encompasses all possible embodiments.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having, “contains,” “containing,” or any othervariation thereof, are intended to cover a non-exclusive inclusion. Acomposition, mixture, process, method, article, or apparatus thatcomprises a list of elements is not necessarily limited to only thoseelements but may include other elements not expressly listed or inherentto such composition, mixture, process, method, article, or apparatus.Further, unless expressly stated to the contrary, “or” refers to aninclusive “or” and not to an exclusive “or.”

The terms “about” and “around,” as used herein to modify a numericalvalue, indicate a close range surrounding that explicit value. If “X”were the value, “about X” or “around X” would indicate a value from 0.9Xto 1.1X, and in certain instances, a value from 0.95X to 1.05X or from0.98X to 1.02X. Any reference to “about X” or “around X” specificallyindicates at least the values X, 0.95X, 0.96X, 0.97X, 0.98X, 0.99X,1.01X, 1.02X, 1.03X, 1.04X, and 1.05X. Thus, “about X” and “around X”are intended to teach and provide written description support for aclaim limitation of, e.g., “0.99X.”

As used herein, the term “pheromone” refers to a substance, orcharacteristic mixture of substances, that is secreted and released byan organism and detected by a second organism of the same species or aclosely related species. Typically, detection of the pheromone by thesecond organism promotes a specific reaction, such as a definitebehavioral reaction or a developmental process. Insect pheromones, forexample, can influence behaviors such as mating and aggregation.Examples of pheromones include, but are not limited to, compoundsproduced by Lepidoptera (i.e., moths and butterflies belonging to theGeometridae, Noctuidae, Arctiidae, and Lymantriidae families) such asC₁₀-C₁₈ acetates, C₁₀-C₁₈ alcohols, C₁₀-C₁₈ aldehydes, and C₁₇-C₂₃polyenes. An “unsaturated pheromone” refers to any pheromone having atleast one carbon-carbon double bond.

As used herein, the term “contacting” refers to the process of bringinginto contact at least two distinct species such that they can react. Itshould be appreciated, however, that the resulting reaction product canbe produced directly from a reaction between the added reagents or froman intermediate from one or more of the added reagents that can beproduced in the reaction mixture.

As used herein, the term “olefin” refers to a straight-chain or branchedhydrocarbon compound containing at least one carbon-carbon double bondand derivatives thereof. The olefin can be unsubstituted or substitutedwith one or more functional groups including alcohol groups, protectedalcohol groups, carboxylate groups, and carboxylic acid ester groups. Asused herein, the term “olefin” encompasses hydrocarbons having more thanone carbon-carbon double bond (e.g., di-olefins, tri-olefins, etc.).Hydrocarbons having more than one carbon-carbon double bond andderivatives thereof are also referred to as “polyenes.” The term “fattyolefin” refers to an olefin having at least four carbon atoms; fattyolefins can have, for example, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24,or 28 carbon atoms. A “fatty olefin derivative” refers to a compoundobtained from an olefin starting material or a fatty olefin startingmaterial. Examples of fatty olefin derivatives include, but are notlimited to, unsaturated fatty alcohols, unsaturated fatty alcoholacetates, unsaturated fatty aldehydes, unsaturated fatty acids,unsaturated fatty acid esters, and polyenes. In certain embodiments,fatty olefins derivatives synthesized according to the methods of theinvention have from 8 to 28 carbon atoms.

A Δ⁹-unsaturated olefin refers to an olefin wherein the ninth bond fromthe end of olefin is a double bond. A Δ⁹-unsaturated fatty acid refersto an olefinic carboxylic acid wherein the ninth bond from thecarboxylic acid group is a double bond. Examples of Δ⁹-unsaturated fattyacids include, but are not limited to, 9-decenoic acid, oleic acid(i.e., (Z)-octadec-9-enoic acid), and elaidic acid (i.e.,(E)-octadec-9-enoic acid).

As used herein, the term “metathesis reaction” refers to a catalyticreaction which involves the interchange of alkylidene units (i.e.,R₂C=units) among compounds containing one or more carbon-carbon doublebonds (e.g., olefinic compounds) via the formation and cleavage of thecarbon-carbon double bonds. Metathesis can occur between two moleculeshaving the same structure (often referred to as self-metathesis) and/orbetween two molecules having different structures (often referred to ascross-metathesis). The term “metathesis reaction partner” refers to acompound having a carbon-carbon double bond that can react with anolefin in a metathesis reaction to form a new carbon-carbon double bond.

As used herein, the term “metathesis catalyst” refers to any catalyst orcatalyst system that catalyzes a metathesis reaction. One of skill inthe art will appreciate that a metathesis catalyst can participate in ametathesis reaction so as to increase the rate of the reaction, but isitself not consumed in the reaction. A “tungsten catalyst” refers to ametathesis catalyst having one or more tungsten atoms. A “molybdenumcatalyst” refers to a metathesis catalyst having one or more molybdenumatoms.

As used herein, the term “metathesis product” refers to an olefincontaining at least one double bond, the bond being formed via ametathesis reaction.

As used herein, the term “converting” refers to reacting a startingmaterial with at least one reagent to form an intermediate species or aproduct. The converting can also include reacting an intermediate withat least one reagent to form a further intermediate species or aproduct.

As used herein, the term “oxidizing” refers to the transfer of electrondensity from a substrate compound to an oxidizing agent. The electrondensity transfer typically occurs via a process including addition ofoxygen to the substrate compound or removal of hydrogen from thesubstrate compound. The term “oxidizing agent” refers to a reagent whichcan accept electron density from the substrate compound. Examples ofoxidizing agents include, but are not limited to, pyridiniumchlorochromate, o-iodoxybenzoic acid, and 2,2,6,6-tetramethylpiperidine1-oxyl.

As used herein, the term “reducing” refers to the transfer of electrondensity from a reducing agent to a substrate compound. The electrondensity transfer typically occurs via a process including addition ofhydrogen to the substrate compound. The term “reducing agent” refers toa reagent which can donate electron density to the substrate compound.Examples of reducing agents include, hut are not limited to, sodiumborohydride and sodium triacetoxyborohydride.

As used herein, the term “acylating” refers to converting a alcoholgroup (—OH), to an ester group (—OC(O)R), where R is an alkyl group asdescribed below.

The term “aliphatic” or “aliphatic group,” as used herein, means astraight-chain (i.e., unbranched) or branched, substituted orunsubstituted hydrocarbon chain that is completely saturated or thatcontains one or more units of unsaturation, or a monocyclic hydrocarbon,bicyclic hydrocarbon, or tricyclic hydrocarbon that is completelysaturated or that contains one or more units of unsaturation, but whichis not aromatic (also referred to herein as “carbocycle” or“cycloaliphatic”), that has a single point of attachment to the rest ofthe molecule. Unless otherwise specified, aliphatic groups contain 1-30aliphatic carbon atoms. In some embodiments, aliphatic groups contain1-20 aliphatic carbon atoms. In other embodiments, aliphatic groupscontain 1-10 aliphatic carbon atoms. In still other embodiments,aliphatic groups contain 1-5 aliphatic carbon atoms, and in yet otherembodiments, aliphatic groups contain 1, 2, 3, or 4 aliphatic carbonatoms. In some embodiments, “cycloaliphatic” (or “carbocycle”) refers toa monocyclic C₃-C₆ hydrocarbon, or a C₈-C₁₀ bicyclic hydrocarbon that iscompletely saturated or that contains one or more units of unsaturation,but which is not aromatic, that has a single point of attachment to therest of the molecule. Suitable aliphatic groups include, but are notlimited to, linear or branched, substituted or unsubstituted alkyl,alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl,(cycloalkenyl)alkyl, or (cycloalkyl)alkenyl. The term “heteroaliphiatic”refers to an aliphatic group wherein at least one carbon atom of thealiphatic group is replaced with a heteroatom (i.e., nitrogen, oxygen,or sulfur, including any oxidized form of nitrogen or sulfur, and anyquaternized form of a basic nitrogen).

As used herein, the term “alkyl” is given its ordinary meaning in theart and includes straight-chain alkyl groups and branched-chain alkylgroups having the number of carbons indicated. In certain embodiments, astraight chain or branched chain alkyl has about 1-30 carbon atoms inits backbone (e.g., C₁-C₃₀ for straight chain, C₃-C₃₀ for branchedchain), and alternatively, about 1-20. In some embodiments, an alkylgroup may be a lower alkyl group, wherein a lower alkyl group comprises1-4 carbon atoms (e.g., C₁-C₄ for straight chain lower alkyls).

The term “heteroalkyl” is given its ordinary meaning in the art andrefers to alkyl groups as described herein in which one or more carbonatoms is replaced with a heteroatom (e.g., oxygen, nitrogen, sulfur, andthe like). Examples of heteroalkyl groups include, but are not limitedto, alkoxy, poly(ethylene glycol)-, alkyl-substituted amino, and thelike.

As used herein, the term “acyl” refers to the functional group —C(O)R),wherein R is an alkyl group as described above.

As used herein, the term “alkoxy” refers to a moiety —OR wherein R is analkyl group as defined above. The term “silylalkyl” refers to an alkylgroup as defined herein wherein as least one carbon atom is replacedwith a silicon atom. The term “silyloxy” refers to a moiety —OSiR₃,wherein each R is independently selected from the group consisting of H,alkyl, substituted alkyl, aryl, and substituted aryl as describedherein.

As used herein, the term “cycloalkyl” refers to a saturated, monocyclichydrocarbon, bicyclic hydrocarbon, or tricyclic hydrocarbon group thathas a single point of attachment to the rest of the molecule. Cycloalkylgroups include alkyl substituted cycloalkyl groups and cycloalkylsubstituted alkyl groups. In some embodiments, cycloalkyl rings havefrom about 3-10 carbon atoms in their ring structure where such ringsare monocyclic or bicyclic, and alternatively about 5, 6 or 7 carbons inthe ring structure.

As used herein, the term “alkenyl” refers to an alkyl group, as definedherein, having one or more double bonds. The term “heteroalkenyl” refersto an alkenyl group wherein one or more carbon atoms is replaced with aheteroatom (i.e., nitrogen, oxygen, or sulfur, including any oxidizedform of nitrogen or sulfur, and any quaternized form of a basicnitrogen).

As used herein, the term “alkenol” refers to a compound having a formulaR—OR′ wherein R is an alkenyl group and R′ is hydrogen or an alcoholprotecting group.

As used herein, the term “alkynyl” refers to an alkyl group, as definedherein, having one or more triple bonds.

The term “aryl” used alone or as part of a larger moiety as in“aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic orbicyclic ring systems having a total of five to fourteen ring members,wherein at least one ring in the system is aromatic and wherein eachring in the system contains 3 to 7 ring members. The term “aryl” may beused interchangeably with the term “aryl ring.” In certain embodimentsof the present invention, “aryl” refers to an aromatic ring system whichincludes, but is not limited to, phenyl, biphenyl, naphthyl, anthracyland the like, which may bear one or more substituents. Also includedwithin the scope of the term “aryl,” as it is used herein, is a group inwhich an aromatic ring is fused to one or more non-aromatic rings, suchas indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, ortetrahydronaphthyl, and the like. The term “aryloxy” refers to a moiety—OR, wherein R is an aryl group as defined above.

The terms “heteroaryl” and “heteroar-,” used alone or as part of alarger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer togroups having 5 to 10 ring atoms (i.e., monocyclic or bicyclic), in someembodiments 5, 6, 9, or 10 ring atoms. In some embodiments, such ringshave 6, 10, or 14 pi electrons shared in a cyclic arrangement; andhaving, in addition to carbon atoms, from one to five heteroatoms. Theterm “heteroatom” refers to nitrogen, oxygen, or sulfur, and includesany oxidized form of nitrogen or sulfur, and any quaternized form of abasic nitrogen. Heteroaryl groups include, without limitation, thienyl,furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl,oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl,thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl,purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and“heteroar-,” as used herein, also include groups in which aheteroaromatic ring is fused to one or more aryl, cycloaliphatic, orheterocyclyl rings, where the radical or point of attachment is on theheteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl,benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl,benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl,quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl,phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl,tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. Aheteroaryl group may be mono- or bicyclic. The term “heteroaryl” may beused interchangeably with the terms “heteroaryl ring,” “heteroarylgroup,” or “heteroaromatic,” any of which terms include rings that areoptionally substituted. The term “heteroaralkyl” refers to an alkylgroup substituted by a heteroaryl, wherein the alkyl and heteroarylportions independently are optionally substituted.

Examples of aryl and heteroaryl groups include, but are not limited to,phenyl, pyrrolyl, furanyl, thiophenyl, imidazolyl, oxazolyl, thiazolyl,triazolyl, pyrazolyl, pyridinyl, pyrazinyl, pyridazinyl and pyrimidinyl,and the like. It should be understood that, when aryl and heteroarylgroups are used as ligands coordinating a metal center, the aryl andheteroaryl groups may have sufficient ionic character to coordinate themetal center. For example, when a heteroaryl group such as pyrrole isused as a nitrogen-containing ligand, as described herein, it should beunderstood that the pyrrole group has sufficient ionic character (e.g.,is sufficiently deprotonated to define a pyrrolyl) to coordinate themetal center. In some cases, the aryl or heteroaryl group may compriseat least one functional group that has sufficient ionic character tocoordinate the metal center, such as a biphenolate group, for example.

As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclicradical,” and “heterocyclic ring” are used interchangeably and refer toa stable 5- to 7-membered monocyclic or 7-10-membered bicyclicheterocyclic moiety that is either saturated or partially unsaturated,and having, in addition to carbon atoms, one or more heteroatoms (e.g.,one to four heteroatoms), as defined above. When used in reference to aring atom of a heterocycle, the term “nitrogen” includes a substitutednitrogen. As an example, in a saturated or partially unsaturated ringhaving 1-3 heteroatoms selected from oxygen, sulfur or nitrogen, thenitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as inpyrrolidinyl), or ⁺NR (as in N-substituted pyrrolidinyl).

A heterocyclic ring can be attached to its pendant group at anyheteroatom or carbon atom that results in a stable structure and any ofthe ring atoms can be optionally substituted. Examples of such saturatedor partially unsaturated heterocyclic radicals include, withoutlimitation, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolidinyl,piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl,decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl,diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. Theterms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclicgroup,” “heterocyclic moiety,” and “heterocyclic radical,” are usedinterchangeably herein, and also include groups in which aheterocyclyl-ring is fused to one or more aryl, heteroaryl, orcycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl,phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may bemono- or bicyclic. The term “heterocyclylalkyl” refers to an alkyl groupsubstituted by a heterocyclyl, wherein the alkyl and heterocyclylportions independently are optionally substituted.

The terms “halogen” and “halo” are used interchangeably to refer to F,Cl, Br, or I.

As used herein, the term “protecting group” refers to a chemical moietythat renders a functional group unreactive, but is also removable so asto restore the functional group. Examples of “alcohol protecting groups”include, but are not limited to, benzyl; tert-butyl; trityl;tert-butyldimethylsilyl (TBDMS; TBS);4,5-dimethoxy-2-nitrobenzyloxycarbonyl (Dmnb); propargyloxycarbonyl(Poc); and the like. Examples of “amine protecting groups” include, butare not limited to, benzyloxycarbonyl; 9-fluorenylmethyloxycarbonyl(Fmoc); tert-butyloxycarbonyl (Boc); allyloxycarbonyl (Alloc); p-toluenesulfonyl (Tos); 2,2,5,7,8-pentamethylchroman-6-sulfonyl (Pmc);2,2,4,6,7-pentamethyl-2,3-dihydrobenzofuran-5-sulfonyl (Pbf);mesityl-2-sulfonyl (Mts); 4-methoxy-2,3,6-trimethylphenylsulfonyl (Mtr);acetamido; phthalimido; and the like. Other alcohol protecting groupsand amine protecting groups are known to those of skill in the artincluding, for example, those described by Green and Wuts (ProtectiveGroups in Organic Synthesis, 4^(th) Ed. 2007, Wiley-Interscience, NewYork).

As described herein, compounds of the invention may contain “optionallysubstituted” moieties. In general, the term “substituted,” whetherpreceded by the term “optionally” or not, means that one or morehydrogens of the designated moiety are replaced with a suitablesubstituent. Unless otherwise indicated, an “optionally substituted”group may have a suitable substituent at each substitutable position ofthe group, and when more than one position in any given structure may besubstituted with more than one substituent selected from a specifiedgroup, the substituent may be either the same or different at everyposition. Combinations of substituents envisioned by this invention aregenerally those that result in the formation of stable or chemicallyfeasible compounds. The term “stable,” as used herein, refers tocompounds that are not substantially altered when subjected toconditions to allow for their production, detection, and, in certainembodiments, their recovery, purification, and use for one or more ofthe purposes disclosed herein.

Suitable monovalent substituents on a substitutable carbon atom of an“optionally substituted” group are independently halogen;—(CH₂)₀₋₄R^(α); —(CH₂)₀₋₄OR^(α); —O(CH₂)₀₋₄R^(α), —O—(CH₂)₀₋₄C(O)OR^(α);—(CH₂)₀₋₄CH(OR^(α))₂; —(CH₂)₀₋₄SR^(α); —(CH₂)₀₋₄Ph, which may besubstituted with R^(α); —(CH₂)₀₋₄O(CH₂)₀₋₁Ph which may be substitutedwith R^(α); —CH═CHPh, which may be substituted with R^(α);—(CH₂)₀₋₄O(CH₂)₀₋₁-pyridyl which may be substituted with R^(α); —NO₂;—CN; —N₃; —(CH₂)₀₋₄N(R^(α))₂; —(CH₂)₀₋₄N(R^(α))C(O)R^(α);—N(R^(α))C(S)R^(α); —(CH₂)₀₋₄N(R^(α))C(O)NR^(α) ₂; —N(R^(α))C(S)NR^(α)₂; —(CH₂)₀₋₄N(R^(α))C(O)OR^(α); —N(R^(α))N(R^(α))C(O)R^(α);—N(R^(α))N(R^(α))C(O)NR^(α) ₂; —N(R^(α))N(R^(α))C(O)OR^(α);—(CH₂)₀₋₄C(O)R^(α); —C(S)R^(α); —(CH₂)₀₋₄C(O)OR^(α);—(CH₂)₀₋₄C(O)SR^(α); —(CH₂)₀₋₄C(O)OSiR^(α) ₃; —(CH₂)₀₋₄OC(O)R^(α);—OC(O)(CH₂)₀₋₄SR—SC(S)SR^(α); —(CH₂)₀₋₄SC(O)R^(α); —(CH₂)₀₋₄C(O)NR^(α)₂; —C(S)NR^(α) ₂, —C(S)SR^(α); —SC(S)SR^(α), —(CH₂)₀₋₄OC(O)NR^(α) ₂;—C(O)N(OR^(α))R^(α); —C(O)C(O)R^(α); —C(O)CH₂C(O)R^(α);—C(NOR^(α))R^(α); —(CH₂)₀₋₄SSR^(α); —(CH₂)₀₋₄S(O)₂R^(α);—(CH₂)₀₋₄S(O)₂OR^(α); —(CH₂)₀₋₄OS(O)₂R^(α); —S(O)₂NR^(α) ₂;—(CH₂)₀₋₄S(O)R^(α); —N(R^(α))S(O)₂NR^(α) ₂; —N(R^(α))S(O)₂R^(α);—N(OR^(α))R^(α); —C(NH)NR^(α) ₂; —P(O)₂R^(α); —P(O)R^(α) ₂; —OP(O)R^(α)₂; —OP(O)(OR^(α))₂; SiR^(α) ₃; —(C₁₋₄ straight orbranched)alkylene)O—N(R^(α))₂; or —(C₁₋₄ straight orbranched)alkylene)C(O)O—N(R^(α))₂, wherein each R^(α) may be substitutedas defined below and is independently hydrogen, C₁₋₆ aliphatic, —CH₂Ph,—O(CH₂)₀₋₁Ph, —CH₂-(5-6 membered heteroaryl ring), or a 5-6-memberedsaturated, partially unsaturated, or aromatic ring having 0-4heteroatoms independently selected from nitrogen, oxygen, and sulfur,or, notwithstanding the definition above, two independent occurrences ofR^(α), taken together with their intervening atom(s), form a3-12-membered saturated, partially unsaturated, or aromatic mono- orbi-cyclic ring having 0-4 heteroatoms independently selected fromnitrogen, oxygen, and sulfur, which may be substituted as defined below.

Suitable monovalent substituents on R^(α) (or the ring formed by takingtwo independent occurrences of R^(α) together with their interveningatoms), are independently halogen, —(CH₂)₀₋₂R^(β); -(haloR^(β));—(CH₂)₀₋₂OH; —(CH₂)₀₋₂OR^(β); —(CH₂)₀₋₂ CH(OR^(β))₂; —O(haloR^(β)); —CN;—N₃; —(CH₂)₀₋₂C(O)R^(β); —(CH₂)₀₋₂C(O)OH; —(CH₂)₀₋₂C(O)OR^(β); —(CH₂)₀₋₂SR^(β); —(CH₂)₀₋₂SH; —(CH₂)₀₋₂NH₂; —(CH₂)₀₋₂ NHR^(β); —(CH₂)₀₋₂NR^(β) ₂;—NO₂; SiR^(β) ₃; —OSiR^(β) ₃; —C(O)SR^(β); —(C₁₋₄ straight or branchedalkylene)C(O)OR^(β); or —SSR^(β); wherein each R^(β) is unsubstituted orwhere preceded by “halo” is substituted only with one or more halogens,and is independently selected from C₁₋₄ aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph,or a 5-6-membered saturated, partially unsaturated, or aromatic ringhaving 0-4 heteroatoms independently selected from nitrogen, oxygen, andsulfur. Suitable divalent substituents on a saturated carbon atom ofR^(α) include ═O and ═S.

Suitable divalent substituents on a saturated carbon atom of an“optionally substituted” group include the following: ═O; ═S; ═NNR^(γ)₂; ═NNHC(O)R^(γ); ═NNHC(O)OR^(γ); ═NNHS(O)₂R^(γ); ═NR^(γ); ═NOR^(γ);—O(C(R^(γ) ₂))₂₋₃O—; or —S(C(R^(γ) ₂))₂₋₃S—; wherein each independentoccurrence of R^(γ) is selected from hydrogen, C₁₋₆ aliphatic which maybe substituted as defined below, or an unsubstituted 5-6-memberedsaturated, partially unsaturated, or aromatic ring having 0-4heteroatoms independently selected from nitrogen, oxygen, and sulfur.Suitable divalent substituents that are bound to vicinal substitutablecarbons of an “optionally substituted” group include: —O(CR^(β) ₂)₂₋₃O—,wherein each independent occurrence of R^(β) is selected from hydrogen,C₁₋₆ aliphatic which may be substituted as defined below, or anunsubstituted 5-6-membered saturated, partially unsaturated, or aromaticring having 0-4 heteroatoms independently selected from nitrogen,oxygen, and sulfur.

Suitable substituents on the aliphatic group of R^(γ) include halogen,—R^(δ), -(haloR^(δ)), —OH, —O(haloR^(δ)), —CN, —C(O)OH, —C(O)OR^(δ),—NH₂, —NHR^(δ), —NR^(δ) ₂, or —NO₂, wherein each R^(δ) is unsubstitutedor where preceded by “halo” is substituted only with one or morehalogens, and is independently C₁₋₄ aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph, ora 5-6-membered saturated, partially unsaturated, or aromatic ring having0-4 heteroatoms independently selected from nitrogen, oxygen, andsulfur.

Suitable substituents on a substitutable nitrogen of an “optionallysubstituted” group include —R^(ε), —NR^(ε) ₂, —C(O)R^(ε), —C(O)OR^(ε),—C(O)C(O)R^(ε), —C(O)CH₂C(O)R^(ε), —S(O)₂R^(ε), —S(O)₂NR^(ε) ₂,—C(S)NR^(ε) ₂, —C(NH)NR^(ε) ₂, or —N(R^(ε))S(O)₂R^(ε); wherein eachR^(ε) is independently hydrogen, C₁₋₆ aliphatic which may be substitutedas defined below, unsubstituted —OPh, or an unsubstituted 5-6-memberedsaturated, partially unsaturated, or aromatic ring having 0-4heteroatoms independently selected from nitrogen, oxygen, and sulfur,or, notwithstanding the definition above, two independent occurrences ofR^(ε), taken together with their intervening atom(s) form anunsubstituted 3-12-membered saturated, partially unsaturated, oraromatic mono- or bicyclic ring having 0-4 heteroatoms independentlyselected from nitrogen, oxygen, and sulfur.

Suitable substituents on the aliphatic group of R^(ε) are independentlyhalogen, —R^(δ), -(haloR^(δ)), —OH, —OR^(δ), —CN, —C(O)OH, —C(O)OR^(δ),—NH₂, —NHR^(δ), —NR^(δ) ₂, or —NO₂, wherein each R^(δ) is unsubstitutedor where preceded by “halo” is substituted only with one or morehalogens, and is independently C₁₋₄ aliphatic, —CH₂Ph, —O(CH₂)₀₋₁Ph, ora 5-6-membered saturated, partially unsaturated, or aromatic ring having0-4 heteroatoms independently selected from nitrogen, oxygen, andsulfur.

In some embodiments, the term “substituted” is contemplated to includeall permissible substituents of organic compounds, “permissible” beingin the context of the chemical rules of valence known to those ofordinary skill in the art. In some cases, “substituted” may generallyrefer to replacement of a hydrogen atom with a substituent as describedherein. However, “substituted,” as used herein, does not encompassreplacement and/or alteration of a key functional group by which amolecule is identified, e.g., such that the “substituted” functionalgroup becomes, through substitution, a different functional group. Forexample, a “substituted phenyl” group must still comprise the phenylmoiety and cannot be modified by substitution, in this definition, tobecome, e.g., a cyclohexyl group. In a broad aspect, permissiblesubstituents include acyclic and cyclic, branched and unbranched,carbocyclic and heterocyclic, aromatic and nonaromatic substituents oforganic compounds. Illustrative substituents include, for example, thosedescribed herein. Permissible substituents can be one or more and thesame or different for appropriate organic compounds. For example, asubstituted alkyl group may be CF₃. For purposes of this invention, theheteroatoms such as nitrogen may have hydrogen substituents and/or anypermissible substituents of organic compounds described herein whichsatisfy the valencies of the heteroatoms. This invention is not intendedto be limited in any manner by the permissible substituents of organiccompounds.

Examples of substituents include, but are not limited to, alkyl, aryl,arylalkyl, cyclic alkyl, heterocycloalkyl, hydroxy, alkoxy, aryloxy,perhaloalkoxy, arylalkoxy, heteroaryl, heteroaryloxy, heteroarylalkyl,heteroarylalkoxy, azido, amino, halogen, alkylthio, oxo, acylalkyl,carboxy esters, carboxyl, carboxamido, nitro, acyloxy, aminoalkyl,alkylaminoaryl, alkylaryl, alkylaminoalkyl, alkoxyaryl, arylamino,arylalkylamino, alkylsulfonyl, carboxamidoalkylaryl, carboxamidoaryl,hydroxyalkyl, haloalkyl, alkylaminoalkylcarboxy, aminocarboxamidoalkyl,cyano, alkoxyalkyl, perhaloalkyl, arylalkyloxyalkyl, and the like.

As used herein, the term “natural oil” refers to an oil derived from aplant or animal source. The term “natural oil” includes natural oilderivatives, unless otherwise indicated. The plant or animal sources canbe modified plant or animal sources (e.g., genetically modified plant oranimal sources), unless indicated otherwise. Examples of natural oilsinclude, but are not limited to, vegetable oils, algae oils, fish oils,animal fats, tall oils, derivatives of these oils, combinations of anyof these oils, and the like. Representative non-limiting examples ofvegetable oils include canola oil, rapeseed oil, coconut oil, corn oil,cottonseed oil, olive oil, palm oil, peanut oil, safflower oil, sesameoil, soybean oil, sunflower oil, linseed oil, palm kernel oil, tung oil,jatropha oil, mustard oil, pennycress oil, camelina oil, and castor oil.Representative non-limiting examples of animal fats include lard,tallow, poultry fat, yellow grease, and fish oil. Tall oils areby-products of wood pulp manufacture.

“Natural oil derivatives” refer to compounds (or mixtures of compounds)derived from natural oils using any one or combination of methods knownin the art. Such methods include but are not limited to saponification,fat splitting, transesterification, esterification, hydrogenation(partial or full), isomerization, oxidation, reduction, and metathesis.Representative non-limiting examples of natural oil derivatives includegums, phospholipids, soapstock, acidulated soapstock, distillate ordistillate sludge, fatty acids, and fatty acid alkyl esters (e.g.,non-limiting examples such as 2-ethylhexyl ester), and hydroxysubstituted variations thereof. For example, the natural oil derivativemay be a fatty acid methyl ester (“FAME”) derived from the glyceride ofthe natural oil.

The term “contaminant” refers broadly and without limitation to anyimpurity, regardless of the amount in which it is present, admixed witha substrate to be used in olefin metathesis. A “catalyst poisoningcontaminant” refers to a contaminant having the potential to adverselyaffect the performance of a metathesis catalyst. Examples of catalystpoisoning contaminants include, but are not limited to, water,peroxides, and hydroperoxides.

As used herein, the term “metal alkyl compound” refers to a compoundhaving the formula MR_(m) wherein, M is a metal (e.g., a Group II metalor a Group IIIA metal), each R is independently an alkyl radical of 1 toabout 20 carbon atoms, and subscript m corresponds to the valence of M.Examples of metal alkyl compounds include Mg(CH₃)₂, Zn(CH₃)₂, Al(CH₃)₃,and the like. Metal alkyl compounds also include substances having oneor more halogen or hydride groups, such as Grignard reagents,diisobutylaluminum hydride, and the like.

III. Description of the Embodiments

In one aspect, the invention provides a method for synthesizing a fattyolefin derivative. The method includes:

-   -   a) contacting an olefin according to Formula I

-   -   with a metathesis reaction partner according to Formula II

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form a metathesis product; and    -   b) optionally converting the metathesis product to the fatty        olefin derivative;    -   wherein:    -   R¹ is selected from H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl;    -   R² is selected from —(CH₂)_(x)OR^(2a) and —(CH₂)_(y)COOR^(2b),        wherein R^(2a) is an alcohol protecting group and R^(2b) is C₁₋₈        alkyl;    -   subscript x is an integer ranging from 1 to 18;    -   subscript y is an integer ranging from 0 to 17; and    -   subscript z is an integer ranging from 0 to 17.

In some embodiments, the invention provides a method for synthesizing afatty olefin derivative including:

-   -   a) contacting an olefin according to Formula I

-   -   with a metathesis reaction partner according to Formula II

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form a metathesis product; and    -   b) optionally converting the metathesis product to the fatty        olefin derivative;    -   wherein:    -   R¹ is selected from H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl;    -   R² is selected from —(CH₂)_(x)OR^(2a) and —(CH₂)_(y)COOR^(2b),        wherein R^(2a) is an alcohol protecting group and R^(2b) is C₁₋₈        alkyl;    -   subscript x is an integer ranging from 1 to 18;    -   subscript y is an integer ranging from 0 to 17; and    -   subscript z is an integer ranging from 0 to 17;    -   wherein the metathesis catalyst is a tungsten catalyst or a        molybdenum catalyst.

In the methods of the invention, olefins can be reacted with a varietyof metathesis reaction partners to obtain pheromones, pheromoneprecursors, and other useful fatty olefin derivatives.

Metathesis of Fatty Alcohols

Certain embodiments of the method are summarized in Scheme 1. A fattyalcohol containing an appropriate protecting group is reacted with anα-olefin in the presence of a group VI olefin metathesis catalyst (e.g.,a Z-selective Group VI metathesis catalyst) to produce a statisticalmixture of the desired cross-metathesis product and the self-metathesisco-products. The ratio of the feedstocks can be adjusted to vary theratio of products. For example, feeding the reactants in a 1.5:1 molarratio of α-olefin to protected fatty alcohol can result in a 3:2.25:1ratio of the internal olefin, metathesis product, and protected diolproducts. This process condition results in the efficient utilization ofthe more costly protected fatty alcohol.

Products obtained from metathesis of protected fatty alcohols can beconverted to a number of pheromones, as set forth in Table 1.

TABLE 1 Pheromones accessible from fatty alcohol metathesis products.Metathesis Exemplary Pheromone Olefin Reaction Partner MetathesisProduct Pheromone CAS # propylene oleyl alcohol protected(Z)-9-undecenyl 85576-13-2 (Z)-9-undecenol acetate 1-butene oleylalcohol protected (Z)-9-dodecenal 56219-03-5 (Z)-9-dodecenol 1-buteneoleyl alcohol protected (Z)-9-dodecenyl 16974-11-1 (Z)-9-dodecenolacetate 1-pentene oleyl alcohol protected (Z)-9-tridecenyl 35835-78-0(Z)-9-tridecenol acetate 1-hexene oleyl alcohol protected(Z)-9-tetradecenal 53939-27-8 (Z)-9-tetradecenol 1-hexene oleyl alcoholprotected (Z)-9-tetradecenyl 16725-53-4 (Z)-9-tetradecenol acetate1-hexene oleyl alcohol protected (Z)-9-tetradecenyl 56776-10-4(Z)-9-tetradecenol formate 1-hexene oleyl alcohol protected(Z)-9-tetradecenyl 143816-21-1 (Z)-9-tetradecenol nitrate 1-hepteneoleyl alcohol protected (Z)-9-pentadecenyl 64437-41-8 (Z)-9-pentadecenolacetate 1-octene oleyl alcohol protected (Z)-9-hexadecenal 56219-04-6(Z)-9-hexadecenol 1-octene oleyl alcohol protected (Z)-9-hexadecenyl34010-20-3 (Z)-9-hexadecenol acetate propylene 9-decen-1-ol protected(Z)-9-undecenyl 85576-13-2 (Z)-9-undecenol acetate 1-butene 9-decen-1-olprotected (Z)-9-dodecenal 56219-03-5 (Z)-9-dodecenol 1-butene9-decen-1-ol protected (Z)-9-dodecenyl 16974-11-1 (Z)-9-dodecenolacetate 1-pentene 9-decen-1-ol protected (Z)-9-tridecenyl 35835-78-0(Z)-9-tridecenol acetate 1-hexene 9-decen-1-ol protected(Z)-9-tetradecenal 53939-27-8 (Z)-9-tetradecenol 1-hexene 9-decen-1-olprotected (Z)-9-tetradecenyl 16725-53-4 (Z)-9-tetradecenol acetate1-hexene 9-decen-1-ol protected (Z)-9-tetradecenyl 56776-10-4(Z)-9-tetradecenol formate 1-hexene 9-decen-1-ol protected(Z)-9-tetradecenyl 143816-21-1 (Z)-9-tetradecenol nitrate 1-heptene9-decen-1-ol protected (Z)-9-pentadecenyl 64437-41-8 (Z)-9-pentadecenolacetate 1-octene 9-decen-1-ol protected (Z)-9-hexadecenal 56219-04-6(Z)-9-hexadecenol 1-octene 9-decen-1-ol protected (Z)-9-hexadecenyl34010-20-3 (Z)-9-hexadecenol acetate propylene 10-undecen-1-ol protected(Z)-10-dodecenyl 35148-20-0 (Z)-10-dodecenol acetate 1-butene10-undecen-1-ol protected (Z)-10-tridecenyl 64437-24-7 (Z)-10-tridecenolacetate 1-pentene 10-undecen-1-ol protected (Z)-10-tetradecenyl35153-16-3 (Z)-10-tetradecenol acetate 1-hexene 10-undecen-1-olprotected (Z)-10-pentadecenal 60671-80-9 (Z)-10-pentadecenol 1-hexene10-undecen-1-ol protected (Z)-10-pentadecenyl 64437-43-0(Z)-10-pentadecenol acetate 1-heptene 10-undecen-1-ol protected(Z)-10-hexadecenyl 56218-71-4 (Z)-10-hexadecenol acetate 1-butene8-octen-1-ol protected (Z)-7-decenyl 13857-03-9 (Z)-7-decenol acetate1-pentene 8-octen-1-ol protected (Z)-7-undecenyl — (Z)-7-undecenolacetate 1-hexene 8-octen-1-ol protected (E)-7-dodecenal 60671-75-2(Z)-7-dodecenol 1-hexene 8-octen-1-ol protected (Z)-7-dodecenyl14959-86-5 (Z)-7-dodecenol acetate 1-octene 8-octen-1-ol protected(Z)-7-tetradecenal 65128-96-3 (Z)-7-tetradecenol 1-octene 8-octen-1-olprotected (Z)-7-tetradecenyl 16974-10-0 (Z)-7-tetradecenol acetate1-decene 8-octen-1-ol protected (Z)-7-hexadecenal 56797-40-1(Z)-7-hexadecenol 1-decene 8-octen-1-ol protected (Z)-7-hexadecenyl23192-42-9 (Z)-7-hexadecenol acetate

Accordingly, some embodiments of the invention provide a method whereinthe metathesis reaction partner is a protected alcohol according toFormula IIa:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and wherein the metathesis product is a compound according to        Formula IIIa:

Any protecting group R^(2a) that is stable under the metathesis reactionconditions can be used in the methods of the invention. Examples ofsuitable protecting groups include, but are not limited to, silyl,tert-butyl, benzyl, and acetyl. In some embodiments, R^(2a) is acetyl.

In some embodiments, converting the metathesis product to the fattyolefin derivative includes removing R^(2a) from the compound of FormulaIIIa to form an alkenol according to Formula Va:

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIa:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and the metathesis product is a compound according to Formula        IIIc:

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIc:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and the metathesis product is a compound according to Formula        IIIc:

Metathesis products of Formula IIIc can be prepared using Z-selectivemetathesis catalysts.

In some embodiments, converting the metathesis product to the fattyolefin derivative includes removing R^(2a) from the compound of FormulaIIIc to form an alkenol according to Formula Vc:

Conversion of Fatty Alcohol Metathesis Products to Fatty OlefinDerivatives

In some embodiments, the alkenol is the fatty olefin derivative. In someembodiments, an alkenol is converted to a desired fatty olefinderivative product via one or more chemical or biochemicaltransformations. In some such embodiments, the fatty olefin derivativeis a pheromone.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes acylating the alkenol of Formula Va,thereby forming a fatty olefin derivative according to Formula VIa:

wherein R^(2c) is C₁₋₆ acyl.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes acylating the alkenol of Formula Vc,thereby forming a fatty olefin derivative according to Formula VIc:

wherein R^(2c) is C₁₋₆ acyl.

Any acylating agent suitable for forming the fatty olefin derivative ofFormula VIa or Formula VIc can be used in the method of the invention.Examples of suitable acylating agents include acid anhydrides (e.g.,acetic anhydride), acid chlorides (e.g., acetyl chloride), activatedesters (e.g., pentafluorophenyl esters of carboxylic acids), andcarboxylic acids used with coupling agents such asdicyclohexylcarbodiimide or carbonyl diimidazole. Typically, 1-10 molarequivalents of the acylating agent with respect to the alkenol will beused. For example, 1-5 molar equivalents of the acylating agent or 1-2molar equivalents of the acylating agent can be used. In someembodiments, around 1.0, 1.1, 1.2, 1.3, 1.4, or 1.5 molar equivalents ofthe acylating agent (e.g., acetic anhydride) with respect to the alkenolis used to form the fatty olefin derivative of Formula VIa or FormulaVIc.

A base can be used to promote acylation of the alkenol by the acylatingagent. Examples of suitable bases include potassium carbonate, sodiumcarbonate, sodium acetate, Huenig's base (i.e.,N,N-diisopropylethylamine), lutidines including 2,6-lutidine (i.e.,2,6-dimethylpyridine), triethylamine, tributylamine, pyridine,2,6-di-tert-butylpyridine, 1,8-diazabicycloundec-7-ene (DBU),quinuclidine, and the collidines. Combinations of two or more bases canbe used. Typically, less than one molar equivalent of base with respectto the alkenol will be employed in the methods of the invention. Forexample, 0.05-0.9 molar equivalents or 0.1-0.5 molar equivalents of thebase can be used. In some embodiments, around 0.05, 0.1, 0.15, or 0.2molar equivalents of the base (e.g., sodium acetate) with respect to thealkenol is used in conjuction with the acylating agent (e.g., aceticanhydride) to form the fatty olefin derivative of Formula VIa or FormulaVIc.

Any suitable solvent can be used for acylating the alkenol. Suitablesolvents include, but are not limited to, toluene, methylene chloride,ethyl acetate, acetonitrile, tetrahydrofuran, benzene, chloroform,diethyl ether, dimethyl formamide, dimethyl sulfoxide, petroleum ether,and mixtures thereof. Alternatively, an alkenol such as 7-octen-1-ol canbe combined with an acylating agent such as acetic anhydride and a basesuch as sodium acetate without an additional solvent. The acylationreaction is typically conducted at temperatures ranging from around 25°C. to about 100° C. for a period of time sufficient to form the fattyolefin derivative of Formula VIa or Formula VIc. The reaction can beconducted for a period of time ranging from a few minutes to severalhours or longer, depending on the particular alkenol and acylating agentused in the reaction. For example, the reaction can be conducted foraround 10 minutes, or around 30 minutes, or around 1 hour, or around 2hours, or around 4 hours, or around 8 hours, or around 12 hours ataround 40° C., or around 50° C., or around 60° C., or around 70° C., oraround 80° C.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes oxidizing the alkenol of Formula Va,thereby forming a fatty olefin derivative according to Formula VIIa:

Many insect pheromones are fatty aldehydes or comprise a fatty aldehydecomponent. As such, synthesis of certain pheromones includes theconversion of alkenols prepared according to the methods of theinvention to fatty aldehydes. In some embodiments, converting themetathesis product to the fatty olefin derivative further includesoxidizing the alkenol of Formula Vc, thereby forming a fatty olefinderivative according to Formula VIIc:

Any oxidizing agent suitable for converting the alkenol Formula Va tothe fatty olefin derivative of Formula VIIa or Formula VIIc can be usedin the methods of the invention. Examples of suitable oxidizing agentsinclude, but are not limited to, chromium-based reagents (e.g., chromicacid; Jones reagent—chromium trioxide in aqueous sulfuric acid; Collinsreagent—chromium trioxide pyridine complex; pyridinium dichromate;pyridinium chlorochromate and the like); dimethyl sulfoxide (DMSO)-basedreagents (e.g., DMSO/oxalyl chloride; DMSO/diycyclohexyl-carbodiimide;DMSO/acetic anhydride; DMSO/phosphorous pentoxide; DMSO/trifluoroaceticanhydride; and the like); hypervalent iodine compounds (e.g.,Dess-Martin periodinane; o-iodoxybenzoic acid; and the like);ruthenium-based reagents (e.g., ruthenium tetroxide;tetra-n-propylammonium perruthenate; and the like); and nitroxyl-basedreagents (e.g., TEMPO-2,2,6,6-tetramethylpiperidine 1-oxyl—employed withsodium hypochlorite, bromine, or the like).

Oxidation of fatty alcohols is often achieved, for example, viaselective oxidation via pyridinium chlorochromate (PCC) (Scheme 2).

Alternatively, TEMPO (TEMPO=2,2,6,6-tetramethylpiperidinyl-N-oxyl) andrelated catalyst systems can be used to selectively oxidize alcohols toaldehydes. These methods are described in Ryland and Stahl (2014),herein incorporated by reference in its entirety.

Bio-Oxidation of Terminal Alcohols

The conversion of a fatty alcohol to a fatty aldehyde is known to becatalyzed by alcohol dehydrogenases (ADH) and alcohol oxidases (AOX).Additionally, the conversion of a length C_(n) fatty acid to a C_(n-1)fatty aldehyde is catalyzed by plant α-dioxygenases (α-DOX) (Scheme 3).

In some embodiments, an alcohol oxidase (AOX) is used to catalyze theconversion of a fatty alcohol to a fatty aldehyde. Alcohol oxidasescatalyze the conversion of alcohols into corresponding aldehydes (orketones) with electron transfer via the use of molecular oxygen to formhydrogen peroxide as a by-product. AOX enzymes utilize flavin adeninedinucleotide (FAD) as an essential cofactor and regenerate with the helpof oxygen in the reaction medium. Catalase enzymes may be coupled withthe AOX to avoid accumulation of the hydrogen peroxide via catalyticconversion into water and oxygen.

Based on the substrate specificities, AOXs may be categorized into fourgroups: (a) short chain alcohol oxidase, (b) long chain alcohol oxidase,(c) aromatic alcohol oxidase, and (d) secondary alcohol oxidase (Goswamiet al. 2013). Depending on the chain length of the desired substrate,some member of these four groups are better suited for use in themethods of the invention than others.

Short chain alcohol oxidases (including but not limited to thosecurrently classified as EC 1.1.3.13, Table 2) catalyze the oxidation oflower chain length alcohol substrates in the range of C1-C8 carbons (vander Klei et al. 1991) (Ozimek et al. 2005). Aliphatic alcohol oxidasesfrom methylotrophic yeasts such as Candida boidinii and Komagataellapastoris (formerly Pichia pastoris) catalyze the oxidation of primaryalkanols to the corresponding aldehydes with a preference for unbranchedshort-chain aliphatic alcohols. The most broad substrate specificity isfound for alcohol oxidase from the Pichia pastoris including propargylalcohol, 2-chloroethanol, 2-cyanoethanol (Dienys et al. 2003). The majorchallenge encountered in alcohol oxidation is the high reactivity of thealdehyde product. Utilization of a two liquid phase system(water/solvent) can provide in-situ removal of the aldehyde product fromthe reaction phase before it is further converted to the acid. Forexample, hexanal production from hexanol using Pichia pastoris alcoholoxidase coupled with bovine liver catalase was achieved in a bi-phasicsystem by taking advantage of the presence of a stable alcohol oxidasein aqueous phase (Karra-Chaabouni et al. 2003). For example, alcoholoxidase from Pichia pastoris was able to oxidize aliphatic alcohols ofC6 to C11 when used biphasic organic reaction system (Murray and Duff1990). Methods for using alcohol oxidases in a biphasic system accordingto (Karra-Chaabouni et al. 2003) and (Murray and Duff 1990) areincorporated by reference in their entirety.

Long chain alcohol oxidases (including but not limited to thosecurrently classified as EC 1.1.3.20; Table 3) include fatty alcoholoxidases, long chain fatty acid oxidases, and long chain fatty alcoholoxidases that oxidize alcohol substrates with carbon chain length ofgreater than six (Goswami et al. 2013). Banthorpe et al. reported a longchain alcohol oxidase purified from the leaves of Tanacetum vulgare thatwas able to oxidize saturated and unsaturated long chain alcoholsubstrates including hex-trans-2-en-1-ol and octan-1-ol (Banthorpe 1976)(Cardemil 1978). Other plant species, including Simmondsia chinensis(Moreau, R. A., Huang 1979), Arabidopsis thaliana (Cheng et al. 2004),and Lotus japonicas (Zhao et al. 2008) have also been reported assources of long chain alcohol oxidases. Fatty alcohol oxidases aremostly reported from yeast species (Hommel and Ratledge 1990) (Vanhanenet al. 2000) (Hommel et al. 1994) (Kemp et al. 1990) and these enzymesplay an important role in long chain fatty acid metabolism (Cheng et al.2005). Fatty alcohol oxidases from yeast species that degrade and growon long chain alkanes and fatty acid catalyze the oxidation of fattyalcohols. Fatty alcohol oxidase from Candida tropicalis has beenisolated as microsomal cell fractions and characterized for a range ofsubstrates (Eirich et al. 2004) (Kemp et al. 1988) (Kemp et al. 1991)(Mauersberger et al. 1992). Significant activity is observed for primaryalcohols of length C₈ to C₁₆ with reported K_(M) in the 10-50 μM range(Eirich et al. 2004). Alcohol oxidases described may be used for theconversion of medium chain aliphatic alcohols to aldehydes as described,for example, for whole-cells Candida boidinii (Gabelman and Luzio 1997),and Pichia pastoris (Duff and Murray 1988) (Murray and Duff 1990). Longchain alcohol oxidases from filamentous fungi were produced duringgrowth on hydrocarbon substrates (Kumar and Goswami 2006) (Savitha andRatledge 1991). The long chain fatty alcohol oxidase (LjFAO1) from Lotusjaponicas has been heterologously expressed in E. coli and exhibitedbroad substrate specificity for alcohol oxidation including 1-dodecanoland 1-hexadecanol (Zhao et al. 2008).

TABLE 2 Alcohol oxidase enzymes capable of oxidizing short chainalcohols (EC 1.1.3.13). Organism Gene names Accession No. Komagataellapastoris (strain ATCC 76273/CBS 7435/CECT AOX1 PP7435_Chr4-0130 F2QY2711047/NRRL Y-11430/Wegner 21-1) (Yeast) (Pichia pastoris) Komagataellapastoris (strain GS115/ATCC 20864) AOX1 PAS_chr4_0821 P04842 (Yeast)(Pichia pastoris) Komagataella pastoris (strain ATCC 76273/CBS 7435/CECTAOX2 PP7435_Chr4-0863 F2R038 11047/NRRL Y-11430/Wegner 21-1) (Yeast)(Pichia pastoris) Komagataella pastoris (strain GS115/ATCC 20864) AOX2PAS_chr4_0152 C4R702 (Yeast) (Pichia pastoris) Candida boidinii (Yeast)AOD1 Q00922 Pichia angusta (Yeast) (Hansenula polymorpha) MOX P04841Thanatephorus cucumeris (strain AG1-IB/isolate AOD1 BN14_10802 M5CC527/3/14) (Lettuce bottom rot fungus) (Rhizoctonia solani) Thanatephoruscucumeris (strain AG1-IB/isolate MOX BN14_12214 M5CF32 7/3/14) (Lettucebottom rot fungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate AOD1 BN14_10691 M5CAV1 7/3/14) (Lettuce bottom rotfungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate AOD1 BN14_09479 M5C7F4 7/3/14) (Lettuce bottom rotfungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate AOD1 BN14_10803 M5CB66 7/3/14) (Lettuce bottom rotfungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate AOD1 BN14_09900 M5C9N9 7/3/14) (Lettuce bottom rotfungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate AOD1 BN14_08302 M5C2L8 7/3/14) (Lettuce bottom rotfungus) (Rhizoctonia solani) Thanatephorus cucumeris (strainAG1-IB/isolate MOX BN14_09408 M5C784 7/3/14) (Lettuce bottom rot fungus)(Rhizoctonia solani) Thanatephorus cucumeris (strain AG1-IB/isolate MOXBN14_09478 M5C8F8 7/3/14) (Lettuce bottom rot fungus) (Rhizoctoniasolani) Thanatephorus cucumeris (strain AG1-IB/isolate AOD1 BN14_11356M5CH40 7/3/14) (Lettuce bottom rot fungus) (Rhizoctonia solani) Ogataeahenricii AOD1 A5LGF0 Candida methanosorbosa AOD1 A5LGE5 Candidamethanolovescens AOD1 A5LGE4 Candida succiphila AOD1 A5LGE6 Aspergillusniger (strain CBS 513.88/FGSC A1513) An15g02200 A2R501 Aspergillus niger(strain CBS 513.88/FGSC A1513) An18g05480 A2RB46 Moniliophthoraperniciosa (Witches'-broom disease I7CMK2 fungus) (Marasmiusperniciosus) Candida cariosilignicola AOD1 A5LGE3 Candida pignaliae AOD1A5LGE1 Candida pignaliae AOD2 A5LGE2 Candida sonorensis AOD1 A5LGD9Candida sonorensis AOD2 A5LGE0 Pichia naganishii AOD1 A5LGF2 Ogataeaminuta AOD1 A5LGF1 Ogataea philodendri AOD1 A5LGF3 Ogataea wickerhamiiAOD1 A5LGE8 Kuraishia capsulata AOD1 A5LGE7 Talaromyces stipitatus(strain ATCC 10500/CBS TSTA_021940 B8MHF8 375.48/QM 6759/NRRL 1006)(Penicillium stipitatum) Talaromyces stipitatus (strain ATCC 10500/CBSTSTA_065150 B8LTH7 375.48/QM 6759/NRRL 1006) (Penicillium stipitatum)Talaromyces stipitatus (strain ATCC 10500/CBS TSTA_065150 B8LTH8375.48/QM 6759/NRRL 1006) (Penicillium stipitatum) Talaromycesstipitatus (strain ATCC 10500/CBS TSTA_000410 B8MSB1 375.48/QM 6759/NRRL1006) (Penicillium stipitatum) Ogataea glucozyma AOD1 A5LGE9 Ogataeaparapolymorpha (strain DL-1/ATCC HPODL_03886 W1QCJ3 26012/NRRL Y-7560)(Yeast) (Hansenula polymorpha) Gloeophyllum trabeum (Brown rot fungus)AOX A8DPS4 Pichia angusta (Yeast) (Hansenula polymorpha) mox1 A6PZG8Pichia trehalophila AOD1 A5LGF4 Pichia angusta (Yeast) (Hansenulapolymorpha) mox1 A6PZG9 Pichia angusta (Yeast) (Hansenula polymorpha)mox1 A6PZG7 Ixodes scapularis (Black-legged tick) (Deer tick)IscW_ISCW017898 B7PIZ7

TABLE 3 Alcohol oxidase enzymes capable of oxidizing long chain alcoholsincluding fatty alcohols (EC 1.1.3.20). Organism Gene names AccessionNo. Lotus japonicus (Lotus comiculatus var. japonicus) FAO1 B5WWZ8Arabidopsis thaliana (Mouse-ear cress) FAO1 At1g03990 F21M11.7 Q9ZWB9Lotus japonicus (Lotus comiculatus var. japonicus) FAO2 B5WWZ9Arabidopsis thaliana (Mouse-ear cress) FAO3 At3g23410 MLM24.14 Q9LW56MLM24.23 Arabidopsis thaliana (Mouse-ear cress) FAO4A At4g19380T5K18.160 O65709 Arabidopsis thaliana (Mouse-ear cress) FAO4B At4g28570T5F17.20 Q94BP3 Microbotryum violaceum (strain p1A1 Lamole) MVLG_06864U5HIL4 (Anther smut fungus) (Ustilago violacea) Ajellomyces dermatitidisATCC 26199 BDFG_03507 T5BNQ0 Gibberella zeae (strain PH-1/ATCC FG06918.1FGSG_06918 I1RS14 MYA-4620/FGSC 9075/NRRL 31084) (Wheat head blightfungus) (Fusarium graminearum) Pichia sorbitophila (strain ATCCMYA-4447/BCRC Piso0_004410 G8Y5E1 22081/CBS 7064/NBRC 10061/NRRLGNLVRS01_PISO0K16268g Y-12695) (Hybrid yeast) GNLVRS01_PISO0L16269gEmericella nidulans (strain FGSC A4/ATCC AN0623.2 ANIA_00623 Q5BFQ738163/CBS 112.46/NRRL 194/M139) (Aspergillus nidulans) Pyrenophoratritici-repentis (strainPt-1C-BFP) PTRG_10154 B2WJW5 (Wheat tan spotfungus) (Drechslera tritici-repentis) Paracoccidioides lutzii (strainATCC MYA-826/Pb01) PAAG_09117 C1HEC6 (Paracoccidioides brasiliensis)Candida parapsilosis (strain CDC 317/ATCC CPAR2_204420 G8BG15 MYA-4646)(Yeast) (Monilia parapsilosis) Pseudozyma brasiliensis (strain GHG001)(Yeast) PSEUBRA_SCAF2g03010 V5GPS6 Candida parapsilosis (strain CDC317/ATCC CPAR2_204430 G8BG16 MYA-4646) (Yeast) (Monilia parapsilosis)Sclerotinia borealis F-4157 SBOR_5750 W9CDE2 Sordaria macrospore (strainATCC SMAC_06361 F7W6K4 MYA-333/DSM 997/K(L3346)/K-hell) Sordariamacrospore (strain ATCC SMAC_01933 F7VSA1 MYA-333/DSM997/K(L3346)/K-hell) Meyerozyma guilliermondii (strain ATCC 6260/CBSPGUG_03467 A5DJL6 566/DSM 6381/JCM 1539/NBRC 10279/NRRL Y-324) (Yeast)(Candida guilliermondii) Trichophyton rubrum CBS 202.88 H107_00669A0A023ATC5 Arthrobotrys oligospora (strain ATCC 24927/CBS AOL_s00097g516G1XJI9 115.81/DSM 1491) (Nematode-trapping fungus) (Didymozoophagaoligospora) Scheffersomyces stipitis (strain ATCC 58785/CBS FAO1PICST_90828 A3LYX9 6054/NBRC 10063/NRRL Y-11545) (Yeast) (Pichiastipitis) Scheffersomyces stipitis (strain ATCC 58785/CBS FAO2 PICST32359 A3LW61 6054/NBRC 10063/NRRL Y-11545) (Yeast) (Pichia stipitis)Aspergillus oryzae (strain 3.042) (Yellow koji mold) Ao3042_09114 I8TL25Fusarium oxysporum (strain Fo5176) (Fusarium FOXB_17532 F9GFU8 vascularwilt) Rhizopus delemar (strain RA 99-880/ATCC RO3G_08271 I1C536MYA-4621/FGSC 9543/NRRL 43880) (Mucormycosis agent) (Rhizopus arrhizusvar. delemar) Rhizopus delemar (strain RA 99-880/ATCC RO3G_00154 I1BGX0MYA-4621/FGSC 9543/NRRL 43880) (Mucormycosis agent) (Rhizopus arrhizusvar. delemar) Fusarium oxysporum (strain Fo5176) (Fusarium FOXB_07532F9FMA2 vascular wilt) Penicillium roqueforti PROQFM164_S02g001772 W6QPY1Aspergillus clavatus (strain ATCC 1007/CBS ACLA_018400 A1CNB5 513.65/DSM816/NCTC 3887/NRRL 1) Arthroderma otae (strain ATCC MYA-4605/CBSMCYG_08732 C5G1B0 113480) (Microsporum canis) Trichophyton tonsurans(strain CBS 112818) (Scalp TESG_07214 F2S8I2 ringworm fungus)Colletotrichum higginsianum (strain IMI 349063) CH063_13441 H1VUE7(Crucifer anthracnose fungus) Ajellomyces capsulatus (strain H143)(Darling's HCDG_07658 C6HN77 disease fungus) (Histoplasma capsulatum)Trichophyton rubrum (strain ATCC TERG_08235 F2T096 MYA-4607/CBS 118892)(Athlete's foot fungus) Cochliobolus heterostrophus (strain C5/ATCCCOCHEDRAFT_1201414 M2UMT9 48332/race O) (Southern corn leaf blightfungus) (Bipolaris maydis) Candida orthopsilosis (strain 90-125) (Yeast)CORT_0D04510 H8X643 Candida orthopsilosis (strain 90-125) (Yeast)CORT_0D04520 H8X644 Candida orthopsilosis (strain 90-125) (Yeast)CORT_0D04530 H8X645 Pseudozyma aphidis DSM 70725 PaG_03027 W3VP49Coccidioides posadasii (strain C735) (Valley fever CPC735_000380 C5P005fungus) Magnaporthe oryzae (strain P131) (Rice blastOOW_P131scaffold01214g15 L7IZ92 fungus) (Pyricularia oryzae) Neurosporatetrasperma (strain FGSC 2508/ATCC NEUTE1DRAFT_82541 F8MKD1MYA-4615/P0657) Hypocrea virens (strain Gv29-8/FGSC 10586)TRIVIDRAFT_54537 G9MMY7 (Gliocladium virens) (Trichoderma virens)Hypocrea virens (strain Gv29-8/FGSC 10586) TRIVIDRAFT_53801 G9MT89(Gliocladium virens) (Trichoderma virens) Aspergillus niger (strain CBS513.88/FGSC An01g09620 A2Q9Z3 A1513) Verticillium dahliae (strainVdLs.17/ATCC VDAG_05780 G2X6J8 MYA-4575/FGSC 10137) (Verticillium wilt)Ustilago maydis (strain 521/FGSC 9021) (Corn UM02023.1 Q4PCZ0 smutfungus) Fusarium oxysporum f. sp. lycopersici MN25 FOWG_13006 W9LNI9Fusarium oxysporum f. sp. lycopersici MN25 FOWG_02542 W9N9Z1 Candidatropicalis (Yeast) FAO1 Q6QIR6 Magnaporthe oryzae (strain 70-15/ATCCMGG_11317 G4MVK1 MYA-4617/FGSC 8958) (Rice blast fungus) (Pyriculariaoryzae) Candida tropicalis (Yeast) faot Q9P8D9 Candida tropicalis(Yeast) FAO2a Q6QIR5 Phaeosphaeria nodorum (strain SN15/ATCC SNOG_02371Q0V0U3 MYA-4574/FGSC 10173) (Glume blotch fungus) (Septoria nodorum)Candida tropicalis (Yeast) FAO2b Q6QIR4 Pestalotiopsis fici W106-1PFICI_11209 W3WU04 Magnaporthe oryzae (strain Y34) (Rice blastOOU_Y34scaffold00240g57 L7IFT5 fungus) (Pyricularia oryzae)Pseudogymnoascus destructans (strain ATCC GMDG_01756 L8G0G6MYA-4855/20631-21) (Bat white-nose syndrome fungus) (Geomycesdestructans) Pseudogymnoascus destructans (strain ATCC GMDG_04950 L8GCY2MYA-4855/20631-21) (Bat white-nose syndrome fungus) (Geomycesdestructans) Mycosphaerella fijiensis (strain CIRAD86) (BlackMYCFIDRAFT_52380 M2Z831 leaf streak disease fungus) (Pseudocercosporafijiensis) Bipolaris oryzae ATCC 44560 COCMIDRAFT_84580 W7A0I8Cladophialophora psammophila CBS 110553 A1O5_08147 W9WTM9 Fusariumoxysporum f. sp. melonis 26406 FOMG_05173 X0AEE6 Fusarium oxysporum f.sp. melonis 26406 FOMG_17829 W9ZBB7 Cyphellophora europaea CBS 101466HMPREF1541_02174 W2S2S5 Aspergillus kawachii (strain NBRC 4308) (WhiteAKAW_00147 G7X626 koji mold) (Aspergillus awamori var. kawachi)Aspergillus terreus (strain NIH 2624/FGSC ATEG_05086 Q0CMJ8 A1156)Coccidioides immitis (strain RS) (Valley fever CIMG_02987 J3KAI8 fungus)Ajellomyces dermatitidis (strain ER-3/ATCC BDCG_04701 C5GLS5 MYA-2586)(Blastomyces dermatitidis) Fusarium oxysporum f. sp. cubense (strainrace 1) FOC1_g10013865 N4U732 (Panama disease fungus) Rhodotorulaglutinis (strain ATCC 204091/IIP RTG_00643 G0SVU8 30/MTCC 1151) (Yeast)Aspergillus niger (strain ATCC 1015/CBS 113.46/FGSC ASPNIDRAFT_35778G3XTM6 A1144/LSHB Ac4/NCTC 3858a/NRRL 328/USDA 3528.7) Candida cloacaefao1 Q9P8D8 Candida cloacae fao2 Q9P8D7 Fusarium oxysporum f. sp.cubense (strain race 1) FOC1_g10006358 N4TUH3 (Panama disease fungus)Candida albicans (strain SC5314/ATCC FAO1 CaO19.13562 Q59RS8 MYA-2876)(Yeast) orf19.13562 Candida albicans (strain SC5314/ATCC FAO1 CaO19.6143 Q59RP0 MYA-2876) (Yeast) orf19.6143 Chaetomium thermophilum(strain DSM CTHT_0018560 G0S2U9 1495/CBS 144.50/IMI 039719) Mucorcircinelloides f. circinelloides (strain HMPREF1544_05296 S2JDN01006PhL) (Mucormycosis agent) (Calyptromyces circinelloides) Mucorcircinelloides f. circinelloides (strain HMPREF1544_05295 S2JYP51006PhL) (Mucormycosis agent) (Calyptromyces circinelloides) Mucorcircinelloides f. circinelloides (strain HMPREF1544_06348 S2JVK91006PhL) (Mucormycosis agent) (Calyptromyces circinelloides) Botryotiniafuckeliana (strain BcDW1) (Noble rot BcDW1_6807 M7UD26 fungus) (Botrytiscinerea) Podospora anserina (strain S/ATCC PODANS_5_13040 B2AFD8MYA-4624/DSM 980/FGSC 10383) (Pleurage anserina) Neosartorya fumigata(strain ATCC AFUA_1G17110 Q4WR91 MYA-4609/Af293/CBS 101355/FGSC A1100)(Aspergillus fumigatus) Fusarium oxysporum f. sp. vasinfectum 25433FOTG_00686 X0MEE6 Fusarium oxysporum f. sp. vasinfectum 25433 FOTG_12485X0LE98 Trichophyton interdigitale H6 H101_06625 A0A022U717 Beauveriabassiana (strain ARSEF 2860) (White BBA_04100 J4UNY3 muscardine diseasefungus) (Tritirachium shiotae) Fusarium oxysporum f. sp.radicis-lycopersici 26381 FOCG_00843 X0GQ62 Fusarium oxysporum f. sp.radicis-lycopersici 26381 FOCG_15170 X0F4T1 Neurospora tetrasperma(strain FGSC 2509/P0656) NEUTE2DRAFT_88670 G4UNN6 Pseudozyma hubeiensis(strain SY62) (Yeast) PHSY_000086 R9NVU1 Lodderomyces elongisporus(strain ATCC LELG_03289 A5E102 11503/CBS 2605/JCM 1781/NBRC 1676/NRRLYB-4239) (Yeast) (Saccharomyces elongisporus) Malassezia globosa (strainATCC MYA-4612/CBS MGL_3855 A8QAY8 7966) (Dandruff-associated fungus)Byssochlamys spectabilis (strain No. 5/NBRC PVAR5_7014 V5GBL6 109023)(Paecilomyces variotii) Ajellomyces capsulatus (strain H88) (Darling'sHCEG_03274 F0UF47 disease fungus) (Histoplasma capsulatum) Trichosporonasahii var. asahii (strain ATCC A1Q1_03669 J6FBP4 90039/CBS 2479/JCM2466/KCTC 7840/NCYC 2677/UAMH 7654) (Yeast) Penicillium oxalicum (strain114-2/CGMCC 5302) PDE_00027 S7Z8U8 (Penicillium decumbens) Fusariumoxysporum f. sp. conglutinans race 2 FOPG_02304 X0IBE3 54008 Fusariumoxysporum f. sp. conglutinans race 2 FOPG_13066 X0H540 54008 Fusariumoxysporum f. sp. raphani 54005 FOQG_00704 X0D1G8 Fusarium oxysporum f.sp. raphani 54005 FOQG_10402 X0C482 Metarhizium acridum (strain CQMa102) MAC_03115 E9DZR7 Arthroderma benhamiae (strain ATCC ARB_02250D4B1C1 MYA-4681/CBS 112371) (Trichophyton mentagrophytes) Fusariumoxysporum f. sp. cubense tropical race 4 FOIG_12161 X0JFI6 54006Fusarium oxysporum f. sp. cubense tropical race 4 FOIG_12751 X0JDU554006 Cochliobolus heterostrophus (strain C4/ATCC COCC4DRAFT_52836N4WZZ0 48331/race T) (Southern corn leaf blight fungus) (Bipolarismaydis) Trichosporon asahii var. asahii (strain CBS 8904) A1Q2_00631K1VZW1 (Yeast) Mycosphaerella graminicola (strain CBS MYCGRDRAFT_37086F9X375 115943/IPO323) (Speckled leaf blotch fungus) (Septoria tritici)Botryotinia fuckeliana (strain T4) (Noble rot fungus) BofuT4_P072020.1G2XQ18 (Botrytis cinerea) Metarhizium anisopliae (strain ARSEF 23/ATCCMAA_05783 E9F0I4 MYA-3075) Cladophialophora carrionii CBS 160.54G647_05801 V9DAR1 Coccidioides posadasii (strain RMSCC CPSG_09174 E9DH75757/Silveira) (Valley fever fungus) Rhodosporidium toruloides (strainNP11) (Yeast) RHTO_06879 M7X159 (Rhodotorula gracilis) Puccinia graminisf. sp. tritici (strain PGTG_10521 E3KIL8 CRL 75-36-700-3/race SCCL)(Black stem rust fungus) Trichophyton rubrum CBS 288.86 H103_00624A0A022WG28 Colletotrichum fioriniae PJ7 CFIO01_08202 A0A010RKZ4Trichophyton rubrum CBS 289.86 H104_00611 A0A022XB46 Cladophialophorayegresii CBS 114405 A1O7_02579 W9WC55 Colletotrichum orbiculare (strain104-T/ATCC Cob_10151 N4VFP3 96160/CBS 514.97/LARS 414/MAFF 240422)(Cucumber anthracnose fungus) (Colletotrichum lagenarium) Drechslerellastenobrocha 248 DRE_03459 W7IDL6 Neosartorya fumigata (strain CEA10/CBSAFUB_016500 B0XP90 144.89/FGSC A1163) (Aspergillus fumigatus) Thielaviaterrestris (strain ATCC 38088/NRRL THITE_2117674 G2R8H9 8126)(Acremonium alabamense) Gibberella fujikuroi (strain CBS 195.34/IMIFFUJ_02948 S0DZP7 58289/NRRL A-6831) (Bakanae and foot rot diseasefungus) (Fusarium fujikuroi) Gibberella fujikuroi (strain CBS 195.34/IMIFFUJ_12030 S0EMC6 58289/NRRL A-6831) (Bakanae and foot rot diseasefungus) (Fusarium fujikuroi) Aspergillus flavus (strain ATCC 200026/FGSCAFLA_109870 B8N941 A1120/NRRL 3357/JCM 12722/SRRC 167) Togninia minima(strain UCR-PA7) (Esca disease UCRPA7_1719 R8BTZ6 fungus)(Phaeoacremonium aleophilum) Ajellomyces dermatitidis (strain ATCC 18188/ BDDG_09783 F2TUC0 CBS 674.68) (Blastomyces dermatitidis) Macrophominaphaseolina (strain MS6) (Charcoal MPH_10582 K2RHA5 rot fungus)Neurospora crassa (strain ATCC 24698/74-OR23-1A/CBS NCU08977 Q7S2Z2708.71/DSM 1257/FGSC 987) Neosartorya fischeri (strain ATCC 1020/DSMNFIA_008260 A1D156 3700/FGSC A1164/NRRL 181) (Aspergillus fischerianus)Fusarium pseudograminearum (strain CS3096) FPSE_11742 K3U9J5 (Wheat andbarley crown-rot fungus) Spathaspora passalidarum (strain NRRLSPAPADRAFT_54193 G3AJP0 Y-27907/11-Y1) Spathaspora passalidarum (strainNRRL SPAPADRAFT_67198 G3ANX7 Y-27907/11-Y1) Trichophyton verrucosum(strain HKI 0517) TRV_07960 D4DL86 Arthroderma gypseum (strain ATCCMYA-4604/CBS MGYG_07264 E4V2J0 118893) (Microsporum gypseum) Hypocreajecorina (strain QM6a) (Trichoderma TRIREDRAFT_43893 G0R7P8 reesei)Trichophyton rubrum MR1448 H110_00629 A0A022Z1G4 Aspergillus ruber CBS135680 EURHEDRAFT_512125 A0A017SPR0 Glarea lozoyensis (strain ATCC20868/MF5171) GLAREA_04397 S3D6C1 Setosphaeria turcica (strain 28A)(Northern leaf SETTUDRAFT_20639 R0K6H8 blight fungus) (Exserohilumturcicum) Paracoccidioides brasiliensis (strain Pb18) PADG_06552 C1GH16Fusarium oxysporum Fo47 FOZG_13577 W9JPG9 Fusarium oxysporum Fo47FOZG_05344 W9KPH3 Trichophyton rubrum MR1459 H113_00628 A0A022ZY09Penicillium marneffei (strain ATCC 18224/CBS PMAA_075740 B6QBY3334.59/QM 7333) Sphaerulina musiva (strain SO2202) (Poplar stemSEPMUDRAFT_154026 M3DAK6 canker fungus) (Septoria musiva) Gibberellamoniliformis (strain M3125/FGSC FVEG_10526 W7N4P8 7600) (Maize ear andstalk rot fungus) (Fusarium verticillioides) Gibberella moniliformis(strain M3125/FGSC FVEG_08281 W7MVR9 7600) (Maize ear and stalk rotfungus) (Fusarium verticillioides) Pseudozyma antarctica (strain T-34)(Yeast) PANT_22d00298 M9MGF2 (Candida antarctica) Paracoccidioidesbrasiliensis (strain Pb03) PABG_07795 C0SJD4 Rhizophagus irregularis(strain DAOM GLOINDRAFT_82554 U9TF61 181602/DAOM 197198/MUCL 43194)(Arbuscular mycorrhizal fungus) (Glomus intraradices) Penicilliumchrysogenum (strain ATCC Pc21g23700 PCH_Pc21g23700 B6HJ58 28089/DSM1075/Wisconsin 54-1255) (Penicillium notatum) Baudoinia compniacensis(strain UAMH 10762) BAUCODRAFT_274597 M2M6Z5 (Angels' share fungus)Hypocrea atroviridis (strain ATCC 20476/IMI TRIATDRAFT_280929 G9NJ32206040) (Trichoderma atroviride) Colletotrichum gloeosporioides (strainCg-14) CGLO_06642 T0LPH0 (Anthracnose fungus) (Glomerella cingulata)Cordyceps militaris (strain CM01) (Caterpillar CCM_02665 G3JB34 fungus)Pyronema omphalodes (strain CBS 100304) PCON_13062 U4LKE9 (Pyronemaconfluens) Colletotrichum graminicola (strain GLRG_08499 E3QR67M1.001/M2/FGSC 10212) (Maize anthracnose fungus) (Glomerellagraminicola) Glarea lozoyensis (strain ATCC 74030/MF5533) M7I_2117H0EHX4 Fusarium oxysporum f. sp. cubense (strain race 4) FOC4_g10002493N1S969 (Panama disease fungus) Fusarium oxysporum f. sp. cubense (strainrace 4) FOC4_g10011461 N1RT80 (Panama disease fungus) Cochliobolussativus (strain ND90Pr/ATCC COCSADRAFT_295770 M2TBE4 201652) (Commonroot rot and spot blotch fungus) (Bipolaris sorokiniana) Mixia osmundae(strain CBS 9802/IAM Mo05571 E5Q_05571 G7E7S3 14324/JCM 22182/KY 12970)Mycosphaerella pini (strain NZE10/CBS 128990) DOTSEDRAFT_69651 N1PXR0(Red band needle blight fungus) (Dothistroma septosporum) Grosmanniaclavigera (strain kw1407/UAMH CMQ_1113 F0XC64 11150) (Blue stain fungus)(Graphiocladiella clavigera) Fusarium oxysporum FOSC 3-a FOYG_03004W9IUE5 Fusarium oxysporum FOSC 3-a FOYG_16040 W9HNP0 Fusarium oxysporumFOSC 3-a FOYG_17058 W9HB31 Nectria haematococca (strain 77-13-4/ATCCNECHADRAFT_37686 C7YQL1 MYA-4622/FGSC 9596/MPVI) (Fusarium solani subsp.pisi) Nectria haematococca (strain 77-13-4/ATCC NECHADRAFT_77262 C7ZJI0MYA-4622/FGSC 9596/MPVI) (Fusarium solani subsp. pisi) Tubermelanosporum (strain Mel28) (Perigord black GSTUM_00010376001 D5GLS0truffle) Ajellomyces dermatitidis (strain SLH14081) BDBG_07633 C5JYI9(Blastomyces dermatitidis) Chaetomium globosum (strain ATCC 6205/CBSCHGG_09885 Q2GQ69 148.51/DSM 1962/NBRC 6347/NRRL 1970) (Soil fungus)Candida tenuis (strain ATCC 10573/BCRC 21748/CBS CANTEDRAFT_108652G3B9Z1 615/JCM 9827/NBRC 10315/NRRL Y-1498/VKM Y-70) (Yeast)Trichophyton rubrum CBS 100081 H102_00622 A0A022VKY4 Pyrenophora teresf. teres (strain 0-1) (Barley net PTT_09421 E3RLZ3 blotch fungus)(Drechslera teres f. teres) Colletotrichum gloeosporioides (strain Naragc5) CGGC5_4608 L2GB29 (Anthracnose fungus) (Glomerella cingulata)Gibberella zeae (Wheat head blight fungus) FG05_06918 A0A016PCS4(Fusarium graminearum) Trichophyton soudanense CBS 452.61 H105_00612A0A022Y6A6 Sclerotinia sclerotiorum (strain ATCC 18683/1980/Ss-1)SS1G_07437 A7EQ37 (White mold) (Whetzelinia sclerotiorum) Fusariumoxysporum f. sp. pisi HDV247 FOVG_14401 W9NWU8 Fusarium oxysporum f. sp.pisi HDV247 FOVG_02874 W9Q5V3 Ustilago hordei (strain U114875-4) (Barleycovered UHOR_03009 I2G1Z4 smut fungus) Sporisorium reilianum (strainSRZ2) (Maize head sr12985 E6ZYF7 smut fungus) Bipolaris zeicola 26-R-13COCCADRAFT_81154 W6YIP8 Melampsora larici-populina (strain98AG31/pathotype MELLADRAFT_78490 F4RUZ8 3-4-7) (Poplar leaf rustfungus) Fusarium oxysporum f. sp. lycopersici (strain 4287/CBSFOXG_01901 J9MG95 123668/FGSC 9935/NRRL 34936) (Fusarium vascular wiltof tomato) Fusarium oxysporum f. sp. lycopersici (strain 4287/CBSFOXG_11941 J9N9S4 123668/FGSC 9935/NRRL 34936) (Fusarium vascular wiltof tomato) Bipolaris victoriae FI3 COCVIDRAFT_39053 W7EMJ8 Debaryomyceshansenii (strain ATCC 36239/CBS DEHA2E04268g Q6BQL4 767/JCM 1990/NBRC0083/IGC 2968) (Yeast) (Torulaspora hansenii) Clavispora lusitaniae(strain ATCC 42720) (Yeast) CLUG_01505 C4XZX3 (Candida lusitaniae)Candida albicans (strain WO-1) (Yeast) CAWG_02023 C4YME4 Trichophytonrubrum MR850 H100_00625 A0A022U0Q2 Candida dubliniensis (strainCD36/ATCC CD36_32890 B9WMC7 MYA-646/CBS 7987/NCPF 3949/NRRL Y-17841)(Yeast) Starmerella bombicola AOX1 A0A024FB95 Thielavia heterothallica(strain ATCC MYCTH_103590 G2QJL7 42464/BCRC 31852/DSM 1799)(Myceliophthora thermophila) Claviceps purpurea (strain 20.1) (Ergotfungus) CPUR_07614 M1WFI4 (Sphacelia segetum) Aspergillus oryzae (strainATCC 42149/RIB 40) AO090023000571 Q2UH61 (Yellow koji mold)Dictyostelium discoideum (Slime mold) DDB_0184181 Q54DT6 DDB_G0292042Triticum urartu (Red wild einkorn) (Crithodium TRIUR3_22733 M7YME5urartu) Solatium tuberosum (Potato) PGSC0003DMG400017211 M1BG07 Oryzasativa subsp. japonica (Rice) OSJNBb0044B19.5 Q8W5P8 LOC_Os10g33540Oryza sativa subsp. japonica (Rice) OJ1234_B11.20 0s02g0621800 Q6K9N5Oryza sativa subsp. japonica (Rice) OSJNBa0001K12.5 Q8W5P3LOC_Os10g33520 Zea mays (Maize) ZEAMMB73_809149 C0P3J6 Citrus ClementinaCICLE_v10011111mg V4S9P4 Citrus Clementina CICLE_v10018992mg V4U4C9Citrus Clementina CICLE_v10004405mg V4S9D3 Citrus ClementinaCICLE_v10004403mg V4RZZ6 Morus notabilis L484_011703 W9RIK0 Morusnotabilis L484_005930 W9RET7 Medicago truncatula (Barrel medic)(Medicago MTR_1g075650 G7I4U3 tribuloides) Arabidopsis thaliana(Mouse-ear cress) Q8LDP0 Medicago truncatula (Barrel medic) (MedicagoMTR_4g081080 G7JF07 tribuloides) Simmondsia chinensis (Jojoba) (Buxuschinensis) L7VFV2 Prunus persica (Peach) (Amygdalus persica)PRUPE_ppa018458mg M5VXL1 Aphanomyces astaci H257_07411 W4GI89Aphanomyces astaci H257_07412 W4GI44 Aphanomyces astaci H257_07411W4GKE3 Aphanomyces astaci H257_07411 W4GK29 Aphanomyces astaciH257_07411 W4GJ79 Aphanomyces astaci H257_07411 W4GI38 Phaeodactylumtricornutum (strain CCAP 1055/1) PHATRDRAFT_48204 B7G6C1 Hordeum vulgarevar. distichum (Two-rowed F2E4R4 barley) Hordeum vulgare var. distichum(Two-rowed F2DZG1 barley) Hordeum vulgare var. distichum (Two-rowedM0YPG7 barley) Hordeum vulgare var. distichum (Two-rowed M0YPG6 barley)Hordeum vulgare var. distichum (Two-rowed F2CUY4 barley) Ricinuscommunis (Castor bean) RCOM_0867830 B9S1S3 Brassica rapa subsp.pekinensis (Chinese cabbage) BRA014947 M4DEM5 (Brassica pekinensis)Ricinus communis (Castor bean) RCOM_0258730 B9SV13 Brassica rapa subsp.pekinensis (Chinese cabbage) BRA001912 M4CCI2 (Brassica pekinensis)Brassica rapa subsp. pekinensis (Chinese cabbage) BRA012548 M4D7T8(Brassica pekinensis) Brassica rapa subsp. pekinensis (Chinese cabbage)BRA024190 M4E5Y6 (Brassica pekinensis) Brassica rapa subsp. pekinensis(Chinese cabbage) BRA015283 M4DFL0 (Brassica pekinensis) Ricinuscommunis (Castor bean) RCOM_1168730 B9SS54 Zea mays (Maize) C4J691 Oryzaglaberrima (African rice) I1P2B7 Zea mays (Maize) B6SXM3 Zea mays(Maize) C0HFU4 Aegilops tauschii (Tausch's goatgrass) (AegilopsF775_19577 R7W4J3 squarrosa) Solanum habrochaites (Wild tomato)(Lycopersicon R9R6T0 hirsutum) Physcomitrella patens subsp. patens(Moss) PHYPADRAFT_124285 A9S535 Physcomitrella patens subsp. patens(Moss) PHYPADRAFT_113581 A9RG13 Physcomitrella patens subsp. patens(Moss) PHYPADRAFT_182504 A9S9A5 Solanum pennellii (Tomato) (LycopersiconR9R6Q1 pennellii) Vitis vinifera (Grape) VIT_02s0087g00630 F6HJ27 Vitisvinifera (Grape) VIT_07s0005g03780 F6HZM3 Vitis vinifera (Grape)VIT_05s0049g01400 F6H8T4 Vitis vinifera (Grape) VITISV_019349 A5AH38Capsella rubella CARUB_v10013046mg R0HIT3 Capsella rubellaCARUB_v10004212mg R0GUX4 Capsella rubella CARUB_v10004208mg R0F3X6Capsella rubella CARUB_v10012453mg R0ILD0 Capsella rubellaCARUB_v10004208mg R0GUX1 Eutrema salsugineum (Saltwater cress)(Sisymbrium EUTSA_v10024496mg V4MD54 salsugineum) Eutrema salsugineum(Saltwater cress) (Sisymbrium EUTSA_v10020141mg V4NM59 salsugineum)Eutrema salsugineum (Saltwater cress) (Sisymbrium EUTSA_v10024496mgV4LUR9 salsugineum) Eutrema salsugineum (Saltwater cress) (SisymbriumEUTSA_v10024528mg V4P767 salsugineum) Eutrema salsugineum (Saltwatercress) (Sisymbrium EUTSA_v10006882mg V4L2P6 salsugineum) Selaginellamoellendorffii (Spikemoss) SELMODRAFT_87684 D8R6Z6 Selaginellamoellendorffii (Spikemoss) SELMODRAFT_87621 D8R6Z5 Selaginellamoellendorffii (Spikemoss) SELMODRAFT_74601 D8QN81 Selaginellamoellendorffii (Spikemoss) SELMODRAFT_73531 D8QN82 Sorghum bicolor(Sorghum) (Sorghum vulgare) Sb04g026390 C5XXS4 SORBIDRAFT_04g026390Sorghum bicolor (Sorghum) (Sorghum vulgare) Sb04g026370 C5XXS1SORBIDRAFT_04g026370 Sorghum bicolor (Sorghum) (Sorghum vulgare)Sb01g019470 C5WYH6 SORBIDRAFT_01g019470 Sorghum bicolor (Sorghum)(Sorghum vulgare) Sb01g019480 C5WYH7 SORBIDRAFT_01g019480 Sorghumbicolor (Sorghum) (Sorghum vulgare) Sb01g019460 C5WYH5SORBIDRAFT_01g019460 Solanum pimpinellifolium (Currant tomato) R9R6J2(Lycopersicon pimpinellifolium) Phaseolus vulgaris (Kidney bean) (Frenchbean) PHAVU_007G124200g V7BGM7 Phaseolus vulgaris (Kidney bean) (Frenchbean) PHAVU_011G136600g V7AI35 Phaseolus vulgaris (Kidney bean) (Frenchbean) PHAVU_001G162800g V7D063 Solanum tuberosum (Potato)PGSC0003DMG400024294 M1C923 Solanum tuberosum (Potato)PGSC0003DMG400018458 M1BKV4 Solanum tuberosum (Potato)PGSC0003DMG400018458 M1BKV3 Glycine max (Soybean) (Glycine hispida)K7LK61 Glycine max (Soybean) (Glycine hispida) K7KXQ9 Populustrichocarpa (Western balsam poplar) POPTR_008s16920g B9HKS3 (Populusbalsamifera subsp. trichocarpa) Picea sitchensis (Sitka spruce) (Pinussitchensis) B8LQ84 Populus trichocarpa (Western balsam poplar)POPTR_0004s24310g U5GKQ5 (Populus balsamifera subsp. trichocarpa)Populus trichocarpa (Western balsam poplar) POPTR_0010s07980g B9HSG9(Populus balsamifera subsp. trichocarpa) Glycine max (Soybean) (Glycinehispida) I1N9S7 Glycine max (Soybean) (Glycine hispida) I1LSK5 Setariaitalica (Foxtail millet) (Panicum italicum) Si034362m.g K4A658 Solanumlycopersicum (Tomato) (Lycopersicon Solyc09g072610.2 K4CUT7 esculentum)Setaria italica (Foxtail millet) (Panicum italicum) Si016380m.g K3YQ38Solanum lycopersicum (Tomato) (Lycopersicon R9R6I9 esculentum) Solanumlycopersicum (Tomato) (Lycopersicon Solyc09g090350.2 K4CW61 esculentum)Solanum lycopersicum (Tomato) (Lycopersicon Solyc08g005630.2 K4CI54esculentum) Solanum lycopersicum (Tomato) (Lycopersicon Solyc08g075240.2K4CMP1 esculentum) Setaria italica (Foxtail millet) (Panicum italicum)Si034359m.g K4A655 Setaria italica (Foxtail millet) (Panicum italicum)Si034354m.g K4A650 Mimulus guttatus (Spotted monkey flower) (YellowMIMGU_mgv1a001896mg A0A022PU07 monkey flower) Mimulus guttatus (Spottedmonkey flower) (Yellow MIMGU_mgv1a022390mg A0A022RAV4 monkey flower)Mimulus guttatus (Spotted monkey flower) (Yellow MIMGU_mgv1a001868mgA0A022S2E6 monkey flower) Mimulus guttatus (Spotted monkey flower)(Yellow MIMGU_mgv1a001883mg A0A022S275 monkey flower) Mimulus guttatus(Spotted monkey flower) (Yellow MIMGU_mgv1a001761mg A0A022QNF0 monkeyflower) Musa acuminata subsp. malaccensis (Wild banana) M0SNA8 (Musamalaccensis) Musa acuminata subsp. malaccensis (Wild banana) M0RUT7(Musa malaccensis) Musa acuminata subsp. malaccensis (Wild banana)M0RUK3 (Musa malaccensis) Saprolegnia diclina VS20 SDRG_10901 T0RG89Brachypodium distachyon (Purple false brome) BRADI3G49085 I1IBP7(Trachynia distachya) Brachypodium distachyon (Purple false brome)BRADI3G28677 I1I4N2 (Trachynia distachya) Brachypodium distachyon(Purple false brome) BRADI3G28657 I1I4N0 (Trachynia distachya) Oryzasativa subsp. indica (Rice) OsI_34012 B8BHG0 Oryza sativa subsp. indica(Rice) OsI_08118 B8AFT8 Oryza sativa subsp. indica (Rice) OsI_34008A2Z8H1 Oryza sativa subsp. indica (Rice) OsI_34014 B8BHG1 Oryza sativasubsp. japonica (Rice) LOC_Os10g33460 Q7XDG3 Oryza sativa subsp.japonica (Rice) Os10g0474800 Q0IX12 Oryza sativa subsp. japonica (Rice)Os10g0474966 C7J7R1 Oryza sativa subsp. japonica (Rice) OSJNBa0001K12.13Q8W5N7 Oryza sativa subsp. japonica (Rice) OsJ_31873 B9G683 Oryza sativasubsp. japonica (Rice) OsJ_31875 B9G684 Oryza sativa subsp. japonica(Rice) OSJNBa0001K12.3 Q8W5P5 Arabidopsis lyrata subsp. lyrata(Lyre-leaved ARALYDRAFT_470376 D7KDA3 rock-cress) Arabidopsis lyratasubsp. lyrata (Lyre-leaved ARALYDRAFT_479855 D7L3B6 rock-cress)Arabidopsis lyrata subsp. lyrata (Lyre-leaved ARALYDRAFT_491906 D7MDA9rock-cress) Arabidopsis lyrata subsp. lyrata (Lyre-leavedARALYDRAFT_914728 D7MGS9 rock-cress)

In some embodiments, an alcohol dehydrogenase (ADH, Table 4) is used tocatalyze the conversion of a fatty alcohol to a fatty aldehyde. A numberof ADHs identified from alkanotrophic organisms, Pseudomonas fluorescensNRRL B-1244 (Hou et al. 1983), Pseudomonas butanovora ATCC 43655(Vangnai and Arp 2001), and Acinetobacter sp. strain M-1 (Tani et al.2000), have shown to be active on short to medium-chain alkyl alcohols(C₂ to C₁₄). Additionally, commercially available ADHs from Sigma, Horseliver ADH and Baker's yeast ADH have detectable activity for substrateswith length C₁₀ and greater. The reported activities for the longerfatty alcohols may be impacted by the difficulties in solubilizing thesubstrates. For the yeast ADH from Sigma, little to no activity isobserved for C₁₂ to C₁₄ aldehydes by (Tani et al. 2000), however,activity for C₁₂ and C₁₆ hydroxy-ω-fatty acids has been observed (Lu etal. 2010). Recently, two ADHs were characterized from Geobacillusthermodenitrificans NG80-2, an organism that degrades C₁₅ to C₃₆ alkanesusing the LadA hydroxylase. Activity was detected from methanol to1-triacontanol (C₃₀) for both ADHs, with 1-octanol being the preferredsubstrate for ADH2 and ethanol for ADH1 (Liu et al. 2009).

The use of ADHs in whole-cell bioconversions has been mostly focused onthe production of chiral alcohols from ketones (Ernst et al. 2005)(Schroer et al. 2007). Using the ADH from Lactobacillus brevis andcoupled cofactor regeneration with isopropanol, Schroer et al. reportedthe production of 797 g of (R)-methyl-3 hydroxybutanoate from methylacetoacetate, with a space time yield of 29 g/L/h (Schroer et al. 2007).Examples of aliphatic alcohol oxidation in whole-cell transformationshave been reported with commercially obtained S. cerevisiae for theconversion of hexanol to hexanal (Presecki et al. 2012) and 2-heptanolto 2-heptanone (Cappaert and Larroche 2004).

TABLE 4 Exemplary alcohol dehydrogenase enzymes. Organism Gene NameAccession No. Bactrocera oleae (Olive fruit fly) (Dacus oleae) ADHQ9NAR7 Cupriavidus necator (Alcaligenes eutrophus) (Ralstonia adh P14940eutropha) Drosophila adiastola (Fruit fly) (Idiomyia adiastola) AdhQ00669 Drosophila affinidisjuncta (Fruit fly) (Idiomyia Adh P21518affinidisjuncta) Drosophila ambigua (Fruit fly) Adh P25139 Drosophilaborealis (Fruit fly) Adh P48584 Drosophila differens (Fruit fly) AdhP22245 Drosophila equinoxialis (Fruit fly) Adh Q9NG42 Drosophilaflavomontana (Fruit fly) Adh P48585 Drosophila guanche (Fruit fly) AdhQ09009 Drosophila hawaiiensis (Fruit fly) Adh P51549 Drosophilaheteroneura (Fruit fly) Adh P21898 Drosophila immigrans (Fruit fly) AdhQ07588 Drosophila insularis (Fruit fly) Adh Q9NG40 Drosophilalebanonensis (Fruit fly) (Scaptodrosophila Adh P10807 lebanonensis)Drosophila mauritiana (Fruit fly) Adh P07162 Drosophila madeirensis(Fruit fly) Adh Q09010 Drosophila mimica (Fruit fly) (Idiomyia mimica)Adh Q00671 Drosophila nigra (Fruit fly) (Idiomyia nigra) Adh Q00672Drosophila orena (Fruit fly) Adh P07159 Drosophila pseudoobscurabogotana (Fruit fly) Adh P84328 Drosophila picticornis (Fruit fly)(Idiomyia picticornis) Adh P23361 Drosophila planitibia (Fruit fly) AdhP23277 Drosophila paulistorum (Fruit fly) Adh Q9U8S9 Drosophilasilvestris (Fruit fly) Adh P23278 Drosophila subobscura (Fruit fly) AdhQ03384 Drosophila teissieri (Fruit fly) Adh P28484 Drosophila tsacasi(Fruit fly) Adh P51550 Fragaria ananassa (Strawberry) ADH P17648 Malusdomestica (Apple) (Pyrus malus) ADH P48977 Scaptomyza albovittata (Fruitfly) Adh P25988 Scaptomyza crassifemur (Fruit fly) (Drosophilacrassifemur) Adh Q00670 Sulfolobus sp. (strain RC3) adh P50381 Zaprionustuberculatus (Vinegar fly) Adh P51552 Geobacillus stearothermophilus(Bacillus stearothermophilus) adh P42327 Drosophila mayaguana (Fruitfly) Adh, Adh2 P25721 Drosophila melanogaster (Fruit fly) Adh, CG3481P00334 Drosophila pseudoobscura pseudoobscura (Fruit fly) Adh, GA17214Q6LCE4 Drosophila simulans (Fruit fly) Adh, GD23968 Q24641 Drosophilayakuba (Fruit fly) Adh, GE19037 P26719 Drosophila ananassae (Fruit fly)Adh, GF14888 Q50L96 Drosophila erecta (Fruit fly) Adh, GG25120 P28483Drosophila grimshawi (Fruit fly) (Idiomyia grimshawi) Adh, GH13025P51551 Drosophila willistoni (Fruit fly) Adh, GK18290 Q05114 Drosophilapersimilis (Fruit fly) Adh, GL25993 P37473 Drosophila sechellia (Fruitfly) Adh, GM15656 Q9GN94 Cupriavidus necator (strain ATCC 17699/H16/DSM428/Stanier adh, H16_A0757 Q0KDL6 337) (Ralstonia eutropha)Mycobacterium tuberculosis (strain CDC 1551/Oshkosh) adh, MT1581 P9WQC2Staphylococcus aureus (strain MW2) adh, MW0568 Q8NXU1 Mycobacteriumtuberculosis (strain ATCC 25618/H37Rv) adh, Rv1530 P9WQC3 Staphylococcusaureus (strain N315) adh, SA0562 Q7A742 Staphylococcus aureus (strainbovine RF122/ET3-1) adh, SAB0557 Q2YSX0 Sulfolobus acidocaldarius(strain ATCC 33909/DSM 639/JCM adh, Saci_2057 Q4J781 8929/NBRC15157/NCIMB 11770) Staphylococcus aureus (strain COL) adh, SACOL0660Q5HI63 Staphylococcus aureus (strain NCTC 8325) adh, Q2G0G1SAOUHSC_00608 Staphylococcus aureus (strain MRSA252) adh, SAR0613 Q6GJ63Staphylococcus aureus (strain MSSA476) adh, SAS0573 Q6GBM4Staphylococcus aureus (strain USA300) adh, SAUSA300_0594 Q2FJ31Staphylococcus aureus (strain Mu50/ATCC 700699) adh, SAV0605 Q99W07Staphylococcus epidermidis (strain ATCC 12228) adh, SE_0375 Q8CQ56Staphylococcus epidermidis (strain ATCC 35984/RP62A) adh, SERP0257Q5HRD6 Sulfolobus solfataricus (strain ATCC 35092/DSM 1617/JCM adh,SSO2536 P39462 11322/P2) Sulfolobus tokodaii (strain DSM 16993/JCM10545/NBRC adh, STK_25770 Q96XE0 100140/7) Anas platyrhynchos (Domesticduck) (Anas boschas) ADH1 P30350 Apteryx australis (Brown kiwi) ADH1P49645 Ceratitis capitata (Mediterranean fruit fly) (Tephritis capitata)ADH1 P48814 Ceratitis cosyra (Mango fruit fly) (Trypeta cosyra) ADH1Q70UN9 Gallus gallus (Chicken) ADH1 P23991 Columba livia (Domesticpigeon) ADH1 P86883 Coturnix coturnix japonica (Japanese quail)(Coturnix ADH1 P19631 japonica) Drosophila hydei (Fruit fly) Adh1 P23236Drosophila montana (Fruit fly) Adh1 P48586 Drosophila mettleri (Fruitfly) Adh1 P22246 Drosophila mulleri (Fruit fly) Adh1 P07161 Drosophilanavojoa (Fruit fly) Adh1 P12854 Geomys attwateri (Attwater's pocketgopher) (Geomys ADH1 Q9Z2M2 bursarius attwateri) Geomys bursarius(Plains pocket gopher) ADH1 Q64413 Geomys knoxjonesi (Knox Jones'spocket gopher) ADH1 Q64415 Hordeum vulgare (Barley) ADH1 P05336Kluyveromyces marxianus (Yeast) (Candida kefyr) ADH1 Q07288 Zea mays(Maize) ADH1 P00333 Mesocricetus auratus (Golden hamster) ADH1 P86885Pennisetum americanum (Pearl millet) (Pennisetum glaucum) ADH1 P14219Petunia hybrida (Petunia) ADH1 P25141 Oryctolagus cuniculus (Rabbit)ADH1 Q03505 Solanum tuberosum (Potato) ADH1 P14673 Struthio camelus(Ostrich) ADH1 P80338 Trifolium repens (Creeping white clover) ADH1P13603 Zea luxurians (Guatemalan teosinte) (Euchlaena luxurians) ADH1Q07264 Saccharomyces cerevisiae (strain ATCC 204508/S288c) ADH1, ADC1,P00330 (Baker's yeast) YOL086C, O0947 Arabidopsis thaliana (Mouse-earcress) ADH1, ADH, P06525 At1g77120, F22K20.19 Schizosaccharomyces pombe(strain 972/ATCC 24843) adh1, adh, P00332 (Fission yeast) SPCC13B11.01Drosophila lacicola (Fruit fly) Adh1, Adh-1 Q27404 Mus musculus (Mouse)Adh1, Adh-1 P00329 Peromyscus maniculatus (North American deer mouse)ADH1, ADH-1 P41680 Rattus norvegicus (Rat) Adh1, Adh-1 P06757 Drosophilavirilis (Fruit fly) Adh1, Adh-1, B4M8Y0 GJ18208 Scheffersomyces stipitis(strain ATCC 58785/CBS 6054/NBRC ADH1, ADH2, O00097 10063/NRRL Y-11545)(Yeast) (Pichia stipitis) PICST_68558 Aspergillus flavus (strain ATCC200026/FGSC A1120/NRRL adh1, AFLA_048690 P41747 3357/JCM 12722/SRRC 167)Neurospora crassa (strain ATCC 24698/74-OR23-1A/CBS adh-1, B17C10.210,Q9P6C8 708.71/DSM 1257/FGSC 987) NCU01754 Candida albicans (Yeast) ADH1,CAD P43067 Oryza sativa subsp. japonica (Rice) ADH1, DUPR11.3, Q2R8Z5Os11g0210300, LOC_Os11g10480, OsJ_032001 Drosophila mojavensis (Fruitfly) Adh1, GI17644 P09370 Kluyveromyces lactis (strain ATCC 8585/CBS2359/DSM ADH1, P20369 70799/NBRC 1267/NRRL Y-1140/WM37) (Yeast)KLLA0F21010g (Candida sphaerica) Oryza sativa subsp. indica (Rice) ADH1,OsI_034290 Q75ZX4 Pongo abelii (Sumatran orangutan) (Pongo pygmaeusabelii) ADH1A Q5RBP7 Homo sapiens (Human) ADH1A, ADH1 P07327 Macacamulatta (Rhesus macaque) ADH1A, ADH1 P28469 Pan troglodytes (Chimpanzee)ADH1B Q5R1W2 Papio hamadryas (Hamadryas baboon) ADH1B P14139 Homosapiens (Human) ADH1B, ADH2 P00325 Homo sapiens (Human) ADH1C, ADH3P00326 Papio hamadryas (Hamadryas baboon) ADH1C, ADH3 O97959 Ceratitiscapitata (Mediterranean fruit fly) (Tephritis capitata) ADH2 P48815Ceratitis cosyra (Mango fruit fly) (Trypeta cosyra) ADH2 Q70UP5Ceratitis rosa (Natal fruit fly) (Pterandrus rosa) ADH2 Q70UP6Drosophila arizonae (Fruit fly) Adh2 P27581 Drosophila buzzatii (Fruitfly) Adh2 P25720 Drosophila hydei (Fruit fly) Adh2 P23237 Drosophilamontana (Fruit fly) Adh2 P48587 Drosophila mulleri (Fruit fly) Adh2P07160 Drosophila wheeleri (Fruit fly) Adh2 P24267 Entamoeba histolyticaADH2 Q24803 Hordeum vulgare (Barley) ADH2 P10847 Kluyveromyces marxianus(Yeast) (Candida kefyr) ADH2 Q9P4C2 Zea mays (Maize) ADH2 P04707 Oryzasativa subsp. indica (Rice) ADH2 Q4R1E8 Solanum lycopersicum (Tomato)(Lycopersicon esculentum) ADH2 P28032 Solanum tuberosum (Potato) ADH2P14674 Scheffersomyces stipitis (strain ATCC 58785/CBS 6054/NBRC ADH2,ADH1, O13309 10063/NRRL Y-11545) (Yeast) (Pichia stipitis) PICST_27980Arabidopsis thaliana (Mouse-ear cress) ADH2, ADHIII, Q96533 FDH1,At5g43940, MRH10.4 Saccharomyces cerevisiae (strain ATCC 204508/S288c)ADH2, ADR2, P00331 (Baker's yeast) YMR303C, YM9952.05C Candida albicans(strain SC5314/ATCC MYA-2876) ADH2, Ca41C10.04, O94038 (Yeast)CaO19.12579, CaO19.5113 Oryza sativa subsp. japonica (Rice) ADH2,DUPR11.1, Q0ITW7 Os11g0210500, LOC_Os11g10510 Drosophila mojavensis(Fruit fly) Adh2, GI17643 P09369 Kluyveromyces lactis (strain ATCC8585/CBS 2359/DSM ADH2, P49383 70799/NBRC 1267/NRRL Y-1140/WM37) (Yeast)KLLA0F18260g (Candida sphaerica) Oryctolagus cuniculus (Rabbit) ADH2-1O46649 Oryctolagus cuniculus (Rabbit) ADH2-2 O46650 Hordeum vulgare(Barley) ADH3 P10848 Solanum tuberosum (Potato) ADH3 P14675Kluyveromyces lactis (strain ATCC 8585/CBS 2359/DSM ADH3, P4938470799/NBRC 1267/NRRL Y-1140/WM37) (Yeast) KLLA0B09064g (Candidasphaerica) Saccharomyces cerevisiae (strain ATCC 204508/S288c) ADH3,YMR083W, P07246 (Baker's yeast) YM9582.08 Homo sapiens (Human) ADH4P08319 Mus musculus (Mouse) Adh4 Q9QYY9 Rattus norvegicus (Rat) Adh4Q64563 Struthio camelus (Ostrich) ADH4 P80468 Kluyveromyces lactis(strain ATCC 8585/CBS 2359/DSM ADH4, P49385 70799/NBRC 1267/NRRLY-1140/WM37) (Yeast) KLLA0F13530g (Candida sphaerica)Schizosaccharomyces pombe (strain 972/ATCC 24843) adh4, SPAC5H10.06cQ09669 (Fission yeast) Saccharomyces cerevisiae (strain YJM789) (Baker'syeast) ADH4, ZRG5, A6ZTT5 SCY_1818 Saccharomyces cerevisiae (strain ATCC204508/S288c) ADH4, ZRG5, P10127 (Baker's yeast) YGL256W, NRC465Saccharomyces pastorianus (Lager yeast) (Saccharomyces ADH5 Q6XQ67cerevisiae × Saccharomyces eubayanus) Bos taurus (Bovine) ADH5 Q3ZC42Equus caballus (Horse) ADH5 P19854 Mus musculus (Mouse) Adh5, Adh-2,Adh2 P28474 Rattus norvegicus (Rat) Adh5, Adh-2, Adh2 P12711 Oryctolaguscuniculus (Rabbit) ADH5, ADH3 O19053 Homo sapiens (Human) ADH5, ADHX,FDH P11766 Dictyostelium discoideum (Slime mold) adh5, Q54TC2DDB_G0281865 Saccharomyces cerevisiae (strain ATCC 204508/S288c) ADH5,YBR145W, P38113 (Baker's yeast) YBR1122 Homo sapiens (Human) ADH6 P28332Peromyscus maniculatus (North American deer mouse) ADH6 P41681 Pongoabelii (Sumatran orangutan) (Pongo pygmaeus abelii) ADH6 Q5R7Z8 Rattusnorvegicus (Rat) Adh6 Q5XI95 Homo sapiens (Human) ADH7 P40394 Rattusnorvegicus (Rat) Adh7 P41682 Mus musculus (Mouse) Adh7, Adh-3, Adh3Q64437 Mycobacterium tuberculosis (strain CDC 1551/Oshkosh) adhA, MT1911P9WQC0 Rhizobium meliloti (strain 1021) (Ensifer meliloti) adhA, RA0704,O31186 (Sinorhizobium meliloti) SMa1296 Mycobacterium tuberculosis(strain ATCC 25618/H37Rv) adhA, Rv1862 P9WQC1 Zymomonas mobilis subsp.mobilis (strain ATCC adhA, ZMO1236 P20368 31821/ZM4/CP4) Mycobacteriumbovis (strain ATCC BAA-935/AF2122/97) adhB, Mb0784c Q7U1B9 Mycobacteriumtuberculosis (strain CDC 1551/Oshkosh) adhB, MT0786 P9WQC6 Mycobacteriumtuberculosis (strain ATCC 25618/H37Rv) adhB, Rv0761c, P9WQC7 MTCY369.06cZymomonas mobilis subsp. mobilis (strain ATCC adhB, ZMO1596 P0DJA231821/ZM4/CP4) Zymomonas mobilis subsp. mobilis (strain ATCC 10988/DSMadhB, Zmob_1541 F8DVL8 424/LMG 404/NCIMB 8938/NRRL B-806/ZM1)Mycobacterium tuberculosis (strain CDC 1551/Oshkosh) adhD, MT3171 P9WQB8Mycobacterium tuberculosis (strain ATCC 25618/H37Rv) adhD, Rv3086 P9WQB9Clostridium acetobutylicum (strain ATCC 824/DSM 792/JCM adhE, aad,CA_P0162 P33744 1419/LMG 5710/VKM B-1787) Escherichia coli (strain K12)adhE, ana, b1241, P0A9Q7 JW1228 Escherichia coli O157:H7 adhE, Z2016,P0A9Q8 ECs1741 Rhodobacter sphaeroides (strain ATCC 17023/2.4.1/NCIBadhI, RHOS4_11650, P72324 8253/DSM 158) RSP_2576 Oryza sativa subsp.indica (Rice) ADHIII, OsI_009236 A2XAZ3 Escherichia coli (strain K12)adhP, yddN, b1478, P39451 JW1474 Geobacillus stearothermophilus(Bacillus stearothermophilus) adhT P12311 Emericella nidulans (strainFGSC A4/ATCC 38163/CBS alcA, AN8979 P08843 112.46/NRRL 194/M139)(Aspergillus nidulans) Emericella nidulans (strain FGSC A4/ATCC38163/CBS alc, AN3741 P54202 112.46/NRRL 194/M139) (Aspergillusnidulans) Emericella nidulans (strain FGSC A4/ATCC 38163/CBS alcC, adh3,AN2286 P07754 112.46/NRRL 194/M139) (Aspergillus nidulans) Arabidopsisthaliana (Mouse-ear cress) At1g22430, F12K8.22 Q9SK86 Arabidopsisthaliana (Mouse-ear cress) At1g22440, F12K8.21 Q9SK87 Arabidopsisthaliana (Mouse-ear cress) At1g32780, F6N18.16 A1L4Y2 Arabidopsisthaliana (Mouse-ear cress) At1g64710, F13O11.3 Q8VZ49 Arabidopsisthaliana (Mouse-ear cress) At4g22110, Q0V7W6 F1N20.210 Arabidopsisthaliana (Mouse-ear cress) At5g24760, Q8LEB2 T4C12_30 Arabidopsisthaliana (Mouse-ear cress) At5g42250, K5J14.5 Q9FH04 Zea mays (Maize)FDH P93629 Drosophila melanogaster (Fruit fly) Fdh, gfd, ODH, P46415CG6598 Bacillus subtilis (strain 168) gbsB, BSU31050 P71017Caenorhabditis elegans H24K24.3 Q17335 Oryza sativa subsp. japonica(Rice) Os02g0815500, Q0DWH1 LOC_Os02g57040, OsJ_008550, P0643F09.4Mycobacterium tuberculosis (strain ATCC 25618/H37Rv) Rv1895 O07737Caenorhabditis elegans sodh-1, K12G11.3 Q17334 Caenorhabditis eleganssodh-2, K12G11.4 O45687 Pseudomonas sp. terPD P33010 Escherichia coli(strain K12) yiaY, b3589, JW5648 P37686 Moraxella sp. (strain TAE123)P81786 Alligator mississippiensis (American alligator) P80222Catharanthus roseus (Madagascar periwinkle) (Vinca rosea) P85440 Gadusmorhua subsp. callarias (Baltic cod) (Gadus callarias) P26325 Naja naja(Indian cobra) P80512 Pisum sativum (Garden pea) P12886 Pelophylaxperezi (Perez's frog) (Rana perezi) P22797 Saara hardwickii (Indianspiny-tailed lizard) (Uromastyx P25405 hardwickii) Saara hardwickii(Indian spiny-tailed lizard) (Uromastyx P25406 hardwickii) Equuscaballus (Horse) P00327 Equus caballus (Horse) P00328 Geobacillusstearothermophilus (Bacillus stearothermophilus) P42328 Gadus morhua(Atlantic cod) P81600 Gadus morhua (Atlantic cod) P81601 Myxineglutinosa (Atlantic hagfish) P80360 Octopus vulgaris (Common octopus)P81431 Pisum sativum (Garden pea) P80572 Saara hardwickii (Indianspiny-tailed lizard) (Uromastyx P80467 hardwickii) Scyliorhinus canicula(Small-spotted catshark) (Squalus P86884 canicula) Sparus aurata(Gilthead sea bream) P79896

In some embodiments, an α-dioxygenase is used to catalyze the conversionof a fatty acid to a fatty aldehyde (Hamberg et al. 2005).Alpha-dioxygenases catalyze the conversion of a C_(n) fatty acid to aC_(n-1) aldehyde and may serve as an alternative to both ADH and AOX forfatty aldehyde production if a fatty acid is used as a biotransformationsubstrate. Due to the chain shortening of the dioxygenase reaction, thisroute requires a different synthesis pathway compared to the ADH and AOXroutes. Biotransformations of E. coli cells expressing a riceα-dioxygenase exhibited conversion of C10, C12, C14 and C16 fatty acidsto the corresponding C_(n-1) aldehydes. With the addition of thedetergent Triton X 100, 3.7 mM of pentadecanal (0.8 g/L) was obtainedafter 3 hours from hexadecanoic acid with 74% conversion (Kaehne et al.2011). Exemplary α-dioxygenases are shown in Table 5.

TABLE 5 Exemplary alpha-dioxygenases. Entry Organism Gene names Q9SGH6Arabidopsis thaliana (Mouse-ear cress) DOX1 DIOX1 PADOX-1 PIOX At3g01420T13O15.6 Q9C9U3 Arabidopsis thaliana (Mouse-ear cress) DOX2 DIOX2At1g73680 F25P22.10 P14550 Homo sapiens (Human) AKR1A1 ALDR1 ALR Q69EZ9Solanum lycopersicum (Tomato) (Lycopersicon LOC543896 esculentum) Q5WM33Solanum lycopersicum (Tomato) (Lycopersicon alpha-DOX2 esculentum)Q69F00 Solanum lycopersicum (Tomato) (Lycopersicon esculentum) D7LAG3Arabidopsis lyrata subsp. lyrata (Lyre-leaved ALPHA-DOX1ARALYDRAFT_317048 rock-cress) D8LJL3 Ectocarpus siliculosus (Brown alga)DOX Esi_0026_0091 E3U9P5 Nicotiana attenuata (Coyote tobacco) adox2Synthesis of Polyenes Via Metathesis Reactions

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIa:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and the metathesis product is a compound according to Formula        IV:

In some embodiments, R¹ is C₂₋₁₈ alkenyl. Such embodiments can providepolyene pheromones as described in more detail below.

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIa:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and the metathesis product is a compound according to Formula        IVc:

In some embodiments, the metathesis reaction partner is a protectedalcohol according to Formula IIc:

-   -   wherein R^(2a) is an alcohol protecting group,    -   and the metathesis product is a compound according to Formula        IVc:

Metathesis of Fatty Acid Esters

Fatty acid alkyl esters (FAAE) can be reduced to either aldehydes oralcohols by the use of well-defined homogenous and heterogeneousmethodologies. Therefore, in some cases it can be useful to producefatty olefin derivatives via Z-selective cross-metathesis of a FAAE withan olefin as shown in Scheme 4.

Products obtained from metathesis of protected fatty acid alkyl esterscan be converted to a number of pheromones, as set forth in Table 6.

TABLE 6 Pheromones accessible from fatty acid alkyl ester metathesisproducts. Exemplary Pheromone Metathesis derived from Pheromone OlefinReaction Partner Metathesis Product Metathesis Product CAS # propyleneoleate (Z)-9-undecenoate (Z)-9-undecenyl acetate 85576-13-2 1-buteneoleate (Z)-9-dodecenoate (Z)-9-dodecenal 56219-03-5 1-butene oleate(Z)-9-dodecenoate (Z)-9-dodecenyl acetate 16974-11-1 1-pentene oleate(Z)-9-tridecenoate (Z)-9-tridecenyl acetate 35835-78-0 1-hexene oleate(Z)-tetradec-9-enoate (Z)-9-tetradecenal 53939-27-8 1-hexene oleate(Z)-tetradec-9-enoate (Z)-9-tetradecenyl 16725-53-4 acetate 1-hexeneoleate (Z)-tetradec-9-enoate (Z)-9-tetradecenyl 56776-10-4 formate1-hexene oleate (Z)-tetradec-9-enoate (Z)-9-tetradecenyl 143816-21-1nitrate 1-heptene oleate (Z)-9-pentadecenoate (Z)-9-pentadecenyl64437-41-8 acetate 1-octene oleate (Z)-9-hexadecenoate (Z)-9-hexadecenal56219-04-6 1-octene oleate (Z)-9-hexadecenoate (Z)-9-hexadecenyl34010-20-3 acetate propylene 9-decenoate (Z)-9-undecenoate(Z)-9-undecenyl acetate 85576-13-2 1-butene 9-decenoate(Z)-9-dodecenoate (Z)-9-dodecenal 56219-03-5 1-butene 9-decenoate(Z)-9-dodecenoate (Z)-9-dodecenyl acetate 16974-11-1 1-pentene9-decenoate (Z)-9-tridecenoate (Z)-9-tridecenyl acetate 35835-78-01-hexene 9-decenoate (Z)-tetradec-9-enoate (Z)-9-tetradecenal 53939-27-81-hexene 9-decenoate (Z)-tetradec-9-enoate (Z)-9-tetradecenyl 16725-53-4acetate 1-hexene 9-decenoate (Z)-tetradec-9-enoate (Z)-9-tetradecenyl56776-10-4 formate 1-hexene 9-decenoate (Z)-tetradec-9-enoate(Z)-9-tetradecenyl 143816-21-1 nitrate 1-heptene 9-decenoate(Z)-9-pentadecenoate (Z)-9-pentadecenyl 64437-41-8 acetate 1-octene9-decenoate (Z)-9-hexadecenoate (Z)-9-hexadecenal 56219-04-6 1-octene9-decenoate (Z)-9-hexadecenoate (Z)-9-hexadecenyl 34010-20-3 acetatepropylene 10-undecenoate (Z)-10-dodecenoate (Z)-10-dodecenyl 35148-20-0acetate 1-butene 10-undecenoate (Z)-10-tridecenoate (Z)-10-tridecenylacetate 64437-24-7 1-pentene 10-undecenoate (Z)-10-tetradecenoate(Z)-10-tetradecenyl 35153-16-3 acetate 1-hexene 10-undecenoate(Z)-10-pentadecenoate (Z)-10-pentadecenal 60671-80-9 1-hexene10-undecenoate (Z)-10-pentadecenoate (Z)-10-pentadecenyl 64437-43-0acetate 1-heptene 10-undecenoate (Z)-10-hexadecenoate (Z)-10-hexadecenyl56218-71-4 acetate

Accordingly, some embodiments of the invention provide methods whereinthe metathesis reaction partner is an ester according to Formula IIb:

-   -   wherein R^(2b) is C₁₋₈ alkyl and subscript y is an integer        ranging from 0 to 17; and    -   wherein the metathesis product is a compound according to        Formula IIIb:

In some embodiments, the metathesis reaction partner is an esteraccording to Formula IIb:

-   -   wherein R^(2b) is C₁₋₈ alkyl and subscript y is an integer        ranging from 0 to 17; and    -   the metathesis product is a compound according to Formula IIIc:

In some embodiments, the metathesis reaction partner is an esteraccording to Formula IIc:

-   -   wherein R^(2b) is C₁₋₈ alkyl and subscript y is an integer        ranging from 0 to 17; and    -   the metathesis product is a compound according to Formula IIIc:

Metathesis products according to Formula IIIc can be prepared using anumber of Z-selective catalysts as described below.

In some embodiments, the methods can be used to prepare productsaccording to Formula IIIb or IIIc wherein y is 0 and z is 4; or y is 1and z is 3; or y is 3 and z is 1; or y is 4 and z is 0; or y is 0 and zis 5; or y is 1 and z is 4; or y is 2 and z is 3; or y is 3 and z is 2;or y is 4 and z is 1; or y is 5 and z is 0; or y is 0 and z is 6; or yis 1 and z is 5; or y is 2 and z is 4; or y is 4 and z is 2; or y is 5and z is 1; or y is 6 and z is 0; or y is 0 and z is 7; or y is 1 and zis 6; or y is 2 and z is 5; or y is 3 and z is 4; or y is 4 and z is 3;or y is 5 and z is 2; or y is 6 and z is 1; or y is 7 and z is 0; or yis 0 and z is 8; or y is 1 and z is 7; or y is 2 and z is 6; or y is 3and z is 5; or y is 5 and z is 3; or y is 6 and z is 2; or y is 7 and zis 1; or y is 8 and z is 0; or y is 0 and z is 9; or y is 1 and z is 8;or y is 2 and z is 7; or y is 3 and z is 6; or y is 4 and z is 5; or yis 5 and z is 4; or y is 6 and z is 3; or y is 7 and z is 2; or y is 8and z is 1; or y is 9 and z is 0; or y is 0 and z is 10; or y is 1 and zis 9; or y is 2 and z is 8; or y is 3 and z is 7; or y is 4 and z is 6;or y is 6 and z is 4; or y is 7 and z is 3; or y is 8 and z is 2; or yis 9 and z is 1; or y is 10 and z is 0; or y is 0 and z is 11; or y is 1and z is 10; or y is 2 and z is 9; or y is 3 and z is 8; or y is 4 and zis 7; or y is 5 and z is 6; or y is 6 and z is 5; or y is 7 and z is 4;or y is 8 and z is 3; or y is 9 and z is 2; or y is 10 and z is 1; or yis 11 and z is 0; or y is 0 and z is 12; or y is 1 and z is 11; or y is2 and z is 10; or y is 3 and z is 9; or y is 4 and z is 8; or y is 5 andz is 7; or y is 7 and z is 5; or y is 8 and z is 4; or y is 9 and z is3; or y is 10 and z is 2; or y is 11 and z is 1; or y is 12 and z is 0;or y is 0 and z is 13; or y is 1 and z is 12; or y is 2 and z is 11; ory is 3 and z is 10; or y is 4 and z is 9; or y is 5 and z is 8; or y is6 and z is 7; or y is 7 and z is 6; or y is 8 and z is 5; or y is 9 andz is 4; or y is 10 and z is 3; or y is 11 and z is 2; or y is 12 and zis 1; or y is 13 and z is 0; or y is 0 and z is 14; or y is 1 and z is13; or y is 2 and z is 12; or y is 3 and z is 11; or y is 4 and z is 10;or y is 5 and z is 9; or y is 6 and z is 8; or y is 8 and z is 6; or yis 9 and z is 5; or y is 10 and z is 4; or y is 11 and z is 3; or y is12 and z is 2; or y is 13 and z is 1; or y is 14 and z is 0; or y is 0and z is 15; or y is 1 and z is 14; or y is 2 and z is 13; or y is 3 andz is 12; or y is 4 and z is 11; or y is 5 and z is 10; or y is 6 and zis 9; or y is 7 and z is 8; or y is 8 and z is 7; or y is 9 and z is 6;or y is 10 and z is 5; or y is 11 and z is 4; or y is 12 and z is 3; ory is 13 and z is 2; or y is 14 and z is 1; or y is 15 and z is 0; or yis 0 and z is 16; or y is 1 and z is 15; or y is 2 and z is 14; or y is3 and z is 13; or y is 4 and z is 12; or y is 5 and z is 11; or y is 6and z is 10; or y is 7 and z is 9; or y is 9 and z is 7; or y is 10 andz is 6; or y is 11 and z is 5; or y is 12 and z is 4; or y is 13 and zis 3; or y is 14 and z is 2; or y is 15 and z is 1; or y is 16 and z is0; or y is 1 and z is 16; or y is 2 and z is 15; or y is 3 and z is 14;or y is 4 and z is 13; or y is 5 and z is 12; or y is 6 and z is 11; ory is 7 and z is 10; or y is 8 and z is 9; or y is 9 and z is 8; or y is10 and z is 7; or y is 11 and z is 6; or y is 12 and z is 5; or y is 13and z is 4; or y is 14 and z is 3; or y is 15 and z is 2; or y is 16 andz is 1; or y is 17 and z is 0; or y is 0 and z is 17; or y is 1 and z is17; or y is 2 and z is 16; or y is 3 and z is 15; or y is 4 and z is 14;or y is 5 and z is 13; or y is 6 and z is 12; or y is 7 and z is 11; ory is 8 and z is 10; or y is 10 and z is 8; or y is 11 and z is 7; or yis 12 and z is 6; or y is 13 and z is 5; or y is 14 and z is 4; or y is15 and z is 3; or y is 16 and z is 2; or y is 17 and z is 1. In someembodiments, both y and z are 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12,13, 14, 15, 16, or 17.

Conversion of Fatty Acid Ester Metathesis Products to Fatty OlefinDerivatives

In some embodiments, converting the metathesis product to the fattyolefin derivative includes reducing the metathesis product of FormulaIIIb to form an alkenol according to Formula Vb:

In some embodiments, converting the metathesis product to the fattyolefin derivative includes reducing the metathesis product of FormulaIIIc to form an alkenol according to Formula Vc:

Any suitable conditions for converting the product of Formula IIIb tothe alkenol of Formula Vb can be used in conjunction with the method ofthe invention. Homogenous or heterogenous conditions can be used.Examples of homogenous conditions include, but are not limited to:hydrogenolysis using ligated precious metal catalysts (Tan, et al. Org.Lett. 2015, 17 (3), 454; Spasyuk, D. et al. J. Am. Chem. Soc. 2015, 137,3743; WO 2014/139030), metal hydride-catalyzed reduction using silanereagents (Mimoun, H. J. Org. Chem. 1999, 64, 2582.; U.S. Pat. No.6,533,960); and reduction using aluminum reagents such as lithiumaluminum hydride, sodium bis(2-methoxyethoxy)aluminumhydride (also knownby the tradename RED-AL), or diisobutyl aluminum hydride (CN 103319704;Chandrasekhar, et al. Tetrahedron Lett. 1998, 39, 909). Unsaturatedfatty alcohols can also be prepared via hydrogenolysis withheterogeneous catalysts, such as ZnO or CuO/ZnO supported on chromite,alumina, or other material. Typically, 1-2 molar equivalents of thereducing agent with respect to the fatty acid ester metathesis productwill be used. In some embodiments, around 1.0, 1.1, 1.2, 1.3, 1.4, or1.5 molar equivalents of the reducing agent with respect to the fattyacid ester is used to form the corresponding alkenol.

Any suitable solvent can be used for reducing the fatty acid estermetathesis product. Suitable solvents include, but are not limited to,toluene, methylene chloride, ethyl acetate, acetonitrile,tetrahydrofuran, benzene, chloroform, diethyl ether, dimethyl formamide,dimethyl sulfoxide, petroleum ether, and mixtures thereof. The reductionreaction is typically conducted at temperatures ranging from around −78°C. to about 25° C. for a period of time sufficient to form the alkenol.The reaction can be conducted for a period of time ranging from a fewminutes to several hours or longer, depending on the particular fattyacid ester and reducing agent used in the reaction. For example, thereduction of a methyl (Z)-tetradec-9-enoate with an aluminum reagent(e.g., sodium bis(2-methoxyethoxy)-aluminumhydride) can be conducted for1-2 hours at a temperature ranging from around 0° C. to around 20° C.

In some embodiments, the alkenol is the fatty olefin derivative. In someembodiments, the alkenol is a pheromone.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes acylating the alkenol of Formula Vb,thereby forming a fatty olefin derivative according to Formula VIb:

wherein R^(2c) is C₁₋₆ acyl. The acylation step can be conducted asdescribed above.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes acylating the alkenol of Formula Vc,thereby forming a fatty olefin derivative according to Formula VIc:

wherein R^(2c) is C₁₋₆ acyl. The acylation step can be conducted asdescribed above.

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes oxidizing the alkenol of Formula Vb,thereby forming a fatty olefin derivative according to Formula VIIb:

In some embodiments, converting the metathesis product to the fattyolefin derivative further includes oxidizing the alkenol of Formula Vc,thereby forming a fatty olefin derivative according to Formula VIIc:

In some embodiments, the metathesis reaction partner is an esteraccording to Formula IIb or Formula IIc as described above, and themetathesis product is a compound according to Formula IV:

In some embodiments, the metathesis reaction partner is an esteraccording to Formula IIb or Formula IIc as described above, and themetathesis product is a compound according to Formula IVc:

In some embodiments, R¹ in Formula IV or Formula IVc is C₂₋₁₈ alkenyl.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative, the method comprising:

-   -   a) contacting an olefin according to Formula I

-   -   with a metathesis reaction partner according to Formula IIb

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form a metathesis product according to Formula        IIIb:

and

-   -   b) converting the metathesis product to the fatty olefin        derivative;    -   wherein:    -   each R¹ is independently selected from the group consisting of        H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl;    -   R^(2b) is C₁₋₈ alkyl;    -   subscript y is an integer ranging from 0 to 17; and        subscript z is an integer ranging from 0 to 17.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, converting the metathesis product to the fattyolefin derivative comprises reducing the metathesis product to form analkenol according to Formula Vb:

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, the alkenol is the fatty olefin derivative.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, converting the metathesis product to the fattyolefin derivative further comprises acylating the alkenol, therebyforming a fatty olefin derivative according to Formula VIb:

wherein R^(2c) is C₁₋₆ acyl.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, R¹ is H, R^(2b) is methyl, subscript y is 7,and subscript z is 3. In some such embodiments, R¹ is H, R^(2b) ismethyl, subscript y is 7, subscript z is 3, and R^(2c) is acetyl.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, converting the metathesis product to the fattyolefin derivative further comprises oxidizing the alkenol, therebyforming a fatty olefin derivative according to Formula VIIb:

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, converting the metathesis product to the fattyolefin derivative further comprises reducing the metathesis product,thereby forming a fatty olefin derivative according to Formula VIIb:

In some embodiments, R¹ is H, R^(2b) is methyl, subscript y is 7, andsubscript z is 3 in the fatty olefin derivative according to FormulaVIIb.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, the olefin has a structure according to FormulaIa:

In some embodiments, subscript z is 3 in the olefin according to FormulaIa.

In some embodiments where the metathesis reaction partner according toFormula IIb is employed, the metathesis product comprises a Z olefin. Insome embodiments, at least about 90% of the olefin is a Z olefin. Insome embodiments, the metathesis catalyst is a Z-selective molybdenumcatalyst or a Z-selective tungsten catalyst as described below. In someembodiments, the metathesis catalyst has a structure according toFormula 2 as described below. In some embodiments, the metathesiscatalyst has a structure according to Formula 2a as described below.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative as described above wherein the olefinaccording to Formula I is a linear C₃-C₁₂ alpha olefin, the metathesisreaction partner according to Formula IIb is a Δ⁹-unsaturated fatty acidalkyl ester, the metathesis catalyst is a Z-selective metathesiscatalyst, and the metathesis product according to Formula IIIb is aC₁₁-C₂₀ (Z)-9-unsaturated fatty acid alkyl ester. In some suchembodiments, converting the metathesis product to the fatty olefinderivative comprises contacting the C₁₁-C₂₀ (Z)-9-unsaturated fatty acidalkyl ester with a reducing agent under conditions sufficient to form aC₁₁-C₂₀ (Z)-9-fatty alcohol. In some such embodiments, the reducingagent is sodium bis(2-methoxyethoxy)aluminum hydride.

In some embodiments, converting the metathesis product to the fattyolefin derivative further comprises contacting the C₁₁-C₂₀ (Z)-9-fattyalcohol with an acylating agent in the presence of a base underconditions sufficient to form an acetate ester of the C₁₁-C₂₀(Z)-9-fatty alcohol. In some such embodiments, the acylating agent isacetic anhydride.

In some embodiments, converting the metathesis product to the fattyolefin derivative further comprises oxidizing the C₁₁-C₂₀ (Z)-9-fattyalcohol to form a C₁₁-C₂₀ (Z)-9-alkenal.

In some embodiments, converting the metathesis product to the fattyolefin derivative comprises contacting the C₁₁-C₂₀ (Z)-9-fatty acidalkyl ester with a reducing agent under conditions sufficient to form aC₁₁-C₂₀ (Z)-9-alkenal. In some such embodiments, the reducing agent isamine-modified sodium bis(2-methoxyethoxy)aluminumhydride. Theamine-modified sodium bis(2-methoxyethoxy)aluminumhydride can begenerated in situ via reaction of the sodiumbis(2-methoxyethoxy)aluminumhydride with either a primary amine orsecondary amine (as described, for example, by Shin, et al. Bull. KoreanChem. Soc. 2014, 35, 2169, which is incorporated herein by reference).In some such embodiments, the metathesis catalyst has a structureaccording to Formula 2a as described below.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative as described above wherein: the fatty acidderivative is (Z)-tetradec-9-en-1-yl acetate; the olefin according toFormula I is hex-1-ene, the metathesis reaction partner according toFormula IIb is a Δ⁹-unsaturated fatty acid alkyl ester, the metathesiscatalyst is a Z-selective metathesis catalyst, and the metathesisproduct according to Formula IIIb is an alkyl ester of(Z)-9-tetradec-9-enoate; and wherein converting the metathesis productto the fatty olefin derivative comprises: contacting the alkyl ester of(Z)-9-tetradec-9-enoate with a reducing agent under conditionssufficient to form (Z)-tetradec-9-en-1-ol, and acylating the(Z)-tetradec-9-en-1-ol to form the (Z)-tetradec-9-en-1-yl acetate.

In some such embodiments, the metathesis reaction partner according toFormula IIb is methyl 9-decenoate and the metathesis product is methyl(Z)-tetradec-9-enoate. In some such embodiments, the reducing agent issodium bis(2-methoxyethoxy)aluminumhydride. In some such embodiments,acylating the (Z)-tetradec-9-en-1-ol comprises contacting the(Z)-tetradec-9-en-1-ol with an acylating agent in the presence of a baseunder conditions sufficient to form (Z)-tetradec-9-en-1-yl acetate. Insome such embodiments, the acylating agent is acetic anhydride. In somesuch embodiments, the metathesis catalyst has a structure according toFormula 2a as described below.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative as described above, wherein the fatty acidderivative is (Z)-tetradec-9-enal, the olefin according to Formula I ishex-1-ene, the metathesis reaction partner according to Formula IIb is aΔ⁹-unsaturated fatty acid alkyl ester, the metathesis catalyst is aZ-selective metathesis catalyst, and the metathesis product according toFormula IIIb is an alkyl ester of (Z)-9-tetradec-9-enoate; and whereinconverting the metathesis product to the fatty olefin derivativecomprises contacting the alkyl ester of (Z)-9-tetradec-9-enoate with areducing agent under conditions sufficient to form the(Z)-tetradec-9-enal. In some such embodiments, the reducing agent isamine-modified sodium bis(2-methoxyethoxy) aluminumhydride. Theamine-modified sodium bis(2-methoxyethoxy) aluminumhydride can begenerated as described above. In some such embodiments, theΔ⁹-unsaturated fatty acid alkyl ester according to Formula IIg is methyl9-decenoate and the metathesis product is methyl (Z)-tetradec-9-enoate.In some such embodiments, the metathesis catalyst has a structureaccording to Formula 2a as described below.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative as described above wherein the fatty acidderivative is (Z)-tetradec-9-enal, the olefin according to Formula I ishex-1-ene, the metathesis reaction partner according to Formula IIb is aΔ⁹-unsaturated fatty acid alkyl ester, the metathesis catalyst is aZ-selective metathesis catalyst, and the metathesis product according toFormula IIIb is an alkyl ester of (Z)-tetradec-9-enoate; and whereinconverting the metathesis product to the fatty olefin derivativecomprises contacting the alkyl ester of (Z)-tetradec-9-enoate with areducing agent under conditions sufficient to form(Z)-tetradec-9-en-1-ol, and oxidizing the (Z)-tetradec-9-en-1-ol to formthe (Z)-tetradec-9-enal. In some such embodiments, the reducing agent issodium bis(2-methoxyethoxy)aluminumhydride. In some such embodiments,the Δ⁹-unsaturated fatty acid alkyl ester according to Formula IIg ismethyl 9-decenoate and the metathesis product is methyl(Z)-tetradec-9-enoate. In some such embodiments, the metathesis catalysthas a structure according to Formula 2a as described below.

In another embodiment, the invention provides a method for synthesizinga fatty olefin derivative according to Formula VIb:

-   -   the method comprising:    -   i) reducing an alkyl ester according to Formula IIb

-   -   to form an alkenol according to Formula VIII

-   -   ii) acylating the alkenol to form an acylated alkenol according        to Formula IX

and

-   -   iii) contacting the acylated alkenol with an olefin according to        Formula I

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form the fatty olefin derivative; wherein:    -   R¹ is selected from the group consisting of H, C₁₋₁₈ alkyl, and        C₂₋₁₈ alkenyl;    -   R^(2b) is C₁₋₈ alkyl,    -   R^(2c) is C₁₋₆ acyl,    -   subscript y is an integer ranging from 0 to 17;    -   subscript z is an integer ranging from 0 to 17; and    -   the metathesis catalyst is a tungsten catalyst or a molybdenum        catalyst.

In some embodiments, R¹ is H, R^(2b) is methyl, R^(2c) is acetyl,subscript y is 7, and subscript z is 3 in the method for synthesizing afatty olefin derivative according to Formula VIb. In some embodiments,the metathesis product comprises an E olefin. In some embodiments, themetathesis product comprises a Z-olefin. In some embodiments, themetathesis catalyst is a Z-selective molybdenum catalyst or aZ-selective tungsten catalyst. In some embodiments, the metathesiscatalyst has a structure according to Formula 2 as described below. Insome embodiments, the metathesis catalyst has a structure according toFormula 2a as described below.

Metathesis Catalysts

The catalysts employed in the present invention generally employ metalswhich can mediate a particular desired chemical reaction. In general,any transition metal (e.g., having d electrons) can be used to form thecatalyst, e.g., a metal selected from one of Groups 3-12 of the periodictable or from the lanthanide series. In some embodiments, the metal isselected from Groups 3-8, or, in some cases, from Groups 4-7. In someembodiments, the metal is selected from Group 6. The term “Group 6”refers to the transition metal group comprising chromium, molybdenum,and tungsten. Additionally, the present invention may also include theformation of heterogeneous catalysts containing forms of these elements(e.g., by immobilizing a metal complex on an insoluble substrate, forexample, silica).

The methods of the invention can be assessed in terms of the selectivityof the metathesis reaction—that is, the extent to which the reactionproduces a particular olefin isomer, whether a Z olefin (i.e., a cisolefin) or an E olefin (i.e., a trans olefin).

In general, Z-selective catalysts provide metathesis products whereingreater than 15% (w/w) of the olefin is a Z olefin. For example, themetathesis product can contain the Z olefin in an amount ranging fromabout 20% to about 100%. The metathesis product can contain the Z olefinin an amount ranging from about 25% to about 95%, or from about 30% toabout 90%, or from about 35% to about 85%, or from about 40% to about80%, or from about 45% to about 75%, or from about 50% to about 70%, orfrom about 55% to about 65%. The metathesis product can contain the Zolefin in an amount ranging from about 15% to about 20%, or from about20% to about 25%, or from about 25% to about 30%, or from about 30% toabout 35%, or from about 35% to about 40%, or from about 40% to about45%, or from about 45% to about 50%, or from about 50% to about 60%, orfrom about 60% to about 65%, or from about 65% to about 70%, or fromabout 70% to about 75%, or from about 75% to about 80%, or from about80% to about 85%, or from about 85% to about 90%, or from about 90% toabout 95%, or from about 95% to about 99%. The metathesis product cancontain the Z olefin in an amount of about 55%, 60%, 65%, 70%, 75%, 80%,85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%,99%, or 100% (w/w).

In general, E-selective catalysts provide metathesis products at leastabout 85% (w/w) of the olefin is an E olefin. For example, themetathesis product can contain the E olefin in an amount ranging fromabout 86% to about 100%. The metathesis product can contain the E olefinin an amount ranging from about 86% to about 99%, or from about 88% toabout 98%, or from about 90% to about 96%, or from about 92% to about94%. The metathesis product can contain the E olefin in an amountranging from about 86% to about 89%, or from about 89% to about 92%, orfrom about 92% to about 95%, or from about 95% to about 98%. Themetathesis product can contain the E olefin in an amount of about 86%,87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100%(w/w).

In some embodiments, the metathesis catalyst has a structure accordingto Formula 1:

-   -   wherein:    -   M is Mo or W;    -   R³ is selected from optionally substituted aryl, optionally        substituted heteroaryl, optionally substituted aliphatic, and        optionally substituted heteroaliphatic;    -   each of R⁴ and R⁵ is independently selected from hydrogen,        optionally substituted aliphatic, optionally substituted        heteroaliphatic, optionally substituted aryl, and optionally        substituted heteroaryl;    -   R⁶ is selected from —O-alkyl, —O-heteroalkyl, —O-aryl,        —O-heteroaryl, —N(R^(n))-alkyl, —N(R^(n))-heteroalkyl,        —N(R^(n))-aryl, and —N(R^(n))-heteroaryl,    -   wherein each R^(n) is independently selected from hydrogen, an        amino protecting group, and optionally substituted alkyl,    -   and wherein R⁶ is optionally substituted; and    -   R⁷ is selected from aryl, heteroaryl, alkyl, heteroalkyl,        cycloalkyl, heterocycloalkyl, —O-alkyl, —O-heteroalkyl, —O-aryl,        and —O-heteroaryl, each of which is optionally substituted, or    -   R⁷ is halogen.

In some embodiments, the metathesis catalyst has a structure accordingto Formula 1 and the metathesis product comprises a Z olefin.

In some embodiments, R⁶ is an optionally substituted asymmetric —O-arylgroup and R⁷ is an optionally substituted heteroaryl group.

In some cases, the metal complex includes one or more oxygen-containingligands lacking a plane of symmetry or nitrogen-containing ligandslacking a plane of symmetry (i.e., asymmetric ligands). In someembodiments, such ligands can coordinate the metal atom via an oxygenatom (e.g., via a hydroxyl group), or other atom of the ligand. Theoxygen-containing ligand can coordinate the metal atom via one site ofthe ligand, i.e., the ligand may be a monodentate ligand.

In some embodiments, a ligand can comprise two sites capable of bindingthe metal center, wherein a first site is bonded to a protecting group,or other group, that may reduce the ability of the first site tocoordinate the metal, and the second site coordinates the metal center.For example, the ligand can be a [1,1′-binaphthalene]-2,2′-diol (BINOL)derivative having two hydroxyl groups, wherein one hydroxyl group isbonded to a protecting group (e.g., a silyl protecting group) andanother hydroxyl group coordinates the metal center.

In some embodiments, an asymmetric oxygen-containing ligand is of thefollowing structure:

wherein:

-   -   R¹³ is an optionally substituted group selected from aryl,        heteroaryl, alkyl, or heteroalkyl;    -   R¹⁴ is hydrogen, —OH, halogen, —OPG, or an optionally        substituted group selected from aliphatic, heteroaliphatic,        aryl, aryloxy, heteroaryl, heteroaryloxy, acyl, and acyloxy;    -   or, together R¹³ and R¹⁴ are joined to form an optionally        substituted partially unsaturated or aryl ring;    -   R¹⁵ is —OH, —OPG, or an optionally substituted amino group;    -   R¹⁶ is hydrogen, halogen, an optionally substituted group        selected from aliphatic, heteroaliphatic, aryl, heteroaryl, or        acyl;    -   each of R¹⁷, R¹⁸, R¹⁹, and R²⁰ is independently aryl,        heteroaryl, aliphatic, heteroaliphatic, or acyl, optionally        substituted;    -   or, together R¹⁷ and R¹⁸ are joined to form an optionally        substituted partially unsaturated or aryl ring;    -   or, together R¹⁹ and R²⁰ are joined to form an optionally        substituted partially unsaturated or aryl ring; and    -   each PG is independently a hydroxyl protecting group.

In some embodiments, R³ is an optionally substituted group selected fromaryl and aliphatic.

In some embodiments, R³ is selected from

wherein each R⁸ is independently hydrogen or a monovalent substituent.

In some embodiments, R⁷ is an optionally substituted group selected from

In some embodiments, R⁶ is an optionally substituted group selected from

In some embodiments, R⁶ is

which is optionally substituted.

In some embodiments, the metathesis catalyst is selected from

-   -   wherein M is Mo or W;    -   each R⁸ is independently selected from halo and alkyl;    -   R⁹ is selected from the group of consisting of alkyl, aryl,        alkenyl, and heteroaryl;    -   each R¹⁰ is independently selected from hydrogen, halo, alkyl,        aryl, and heteroaryl;    -   each R¹¹ is independently selected from halo, alkyl, aryl, and        heteroaryl; and    -   each R¹¹ is independently an optionally substituted alkyl.

In some embodiments, the metathesis catalyst is selected from:

In some embodiments, the metathesis catalyst has a structure accordingto Formula 2:

-   -   wherein:    -   M is Mo or W;    -   R^(3a) is selected from optionally substituted aryl, optionally        substituted heteroaryl, optionally substituted alkyl, optionally        substituted heteroalkyl, optionally substituted cycloalkyl, and        optionally substituted heterocycloalkyl, and    -   R^(4a) and R^(5a) are independently selected from hydrogen,        optionally substituted alkyl, optionally substituted alkenyl,        optionally substituted heteroalkyl, optionally substituted        heteroalkenyl, optionally substituted aryl, and optionally        substituted heteroaryl;    -   R^(7a) is selected from optionally substituted alkyl, optionally        substituted alkoxy, optionally substituted heteroalkyl,        optionally substituted aryl, optionally substituted aryloxy,        optionally substituted heteroaryl, optionally substituted        silylalkyl, and optionally substituted silyloxy; and    -   R^(6a) is R^(8a)—X—, wherein    -   X is O or S and R^(8a) is optionally substituted aryl; or    -   X is O and R^(8a) is SiR^(9a)R^(10a)R^(11a) or        CR^(12a)R^(13a)R^(14a), wherein R^(9a), R^(10a), R^(11a),        R^(12a), R^(13a), and R^(14a) are independently selected from        optionally substituted alkyl and optionally substituted phenyl;        or    -   R^(6a) and R^(7a) are linked together and are bonded to M via        oxygen.

In some embodiments, the metathesis catalyst has a structure accordingto Formula 2 and the metathesis product comprises a Z olefin.

In some embodiments, the catalyst is a compound of Formula 2 wherein:

-   -   R^(7a) is selected from the group consisting of alkyl, alkoxy,        heteroalkyl, aryl, aryloxy, and heteroaryl, each of which is        optionally substituted; and    -   X is O or S and R^(8a) is optionally substituted aryl; or        X is O and R^(8a) is CR^(12a)R^(13a)R^(14a).

In some embodiments, the catalyst is a compound of Formula 2 wherein:

-   -   R^(3a) is selected from the group consisting of        2,6-dimethylphenyl; 2,6-diisopropylphenyl; 2,6-dichlorophenyl;        and adamant-1-yl;    -   R^(4a) is selected from the group consisting of —C(CH₃)₂C₆H₅ and        —C(CH₃)₃;    -   R^(5a) is H;    -   R^(7a) is selected from the group consisting of pyrrol-1-yl;        2,5-dimethyl-pyrrol-1-yl; triphenylsilyloxy;        triisopropylsilyloxy;        2-phenyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy;        2-methyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy;        9-phenyl-fluorene-9-yloxy; 2,6-diphenylphenoxy; and t-butyloxy;        and    -   R^(6a) is R^(8a)—X—, wherein    -   X═O and    -   R^(8a) is phenyl which bears two substituents in the ortho        positions with respect to O, or which bears at least three        substituents, from which two substituents are in the ortho        positions with respect to O and one substituent is in the para        position with respect to O; or    -   R^(8a) is selected from the group consisting of optionally        substituted 8-(naphthalene-1-yl)-naphthalene-1-yl; optionally        substituted 8-phenlynaphthalene-1-yl; optionally substituted        quinoline-8-yl; triphenylsilyl; triisopropylsilyl;        triphenylmethyl; tri(4-methylphenyl)methyl;        9-phenyl-fluorene-9-yl;        2-phenyl-1,1,1,3,3,3-hexafluoro-prop-2-yl;        2-methyl-1,1,1,3,3,3-hexafluoro-prop-2-yl; and t-butyl.

In some embodiments, the catalyst is a compound of Formula 2 wherein:

-   -   R^(7a) is selected from the group consisting of pyrrol-1-yl;        2,5-dimethyl-pyrrol-1-yl; and    -   R^(8a) is phenyl which bears two substituents in the ortho        positions with respect to O, or which bears at least three        substituents, from which two substituents are in the ortho        positions with respect to O and one substituent is in the para        position with respect to O; or    -   R^(8a) is selected from the group consisting of optionally        substituted 8-(naphthalene-1-yl)-naphthalene-1-yl and optionally        substituted 8-phenlynaphthalene-1-yl.

In some embodiments, the catalyst is a compound of Formula 2 wherein R⁴is selected from 4-bromo-2,6-diphenylphenoxy;4-fluoro-2,6-diphenylphenoxy; 4-methyl-2,6-diphenylphenoxy;4-methoxy-2,6-diphenylphenoxy; 4-dimethylamino-2,6-diphenylphenoxy;2,4,6-triphenylphenoxy; 4-fluoro-2,6-dimesitylphenoxy;4-bromo-2,6-di-tert-butylphenoxy; 4-methoxy-2,6-di-tert-butylphenoxy;4-methyl-2,6-di-tert-butylphenoxy; 2,4,6-tri-tert-butylphenoxy;4-bromo-2,3,5,6-tetraphenylphenoxy;4-bromo-2,6-di(4-bromophenyl)-3,5-diphenylphenoxy; 2,6-diphenylphenoxy;2,3,5,6-tetraphenylphenoxy; 2,6-di(tert-butyl)phenoxy;2,6-di(2,4,6-triisopropylphenyl)phenoxy; triphenylsilyloxy;triisopropylsilyloxy; triphenylmethyloxy; tri(4-methyphenyl)methyloxy;2-phenyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy;2-methyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy; 9-phenyl-fluorene-9-yloxy;t-butyloxy;

-   -   wherein TBS is t-butyldimethylsilyl; or

-   -   wherein Me=methyl.

In some embodiments, the metathesis catalyst has a structure accordingto Formula 2a:

-   -   wherein:    -   R^(3a) is aryl, heteroaryl, alkyl, or cycloalkyl, each of which        is optionally substituted;    -   R^(7a) is pyrrolyl, imidazolyl, indolyl, pyrazolyl, azaindolyl,        or indazolyl, each of which is optionally substituted;    -   R^(8a) is optionally substituted aryl;    -   R^(5a) is a hydrogen atom, alkyl, or alkoxy;    -   R^(4b) is a hydrogen atom, —O—(C₁₋₆ alkyl), —CH₂—O—(C₁₋₆ alkyl),        heteroalkoxy, or —N(C₁₋₆ alkyl)₂; and    -   R^(4c) and R^(4d) are independently a hydrogen atom, C₁₋₆ alkyl,        C₁₋₆ alkoxy, a halogen atom, —NO₂, an amide, or a sulfonamide.

In some embodiments, the metathesis catalyst has a structure accordingto Formula 2a and the metathesis product comprises a Z olefin.

In some embodiments, R^(3a) in the metathesis catalyst according toFormula 2a is phenyl, 2,6-dichlorophenyl, 2,6-dimethylphenyl,2,6-diisopropylphenyl, 2-trifluoromethylphenyl, pentafluorophenyl,tert-butyl, or 1-adamantyl.

In some embodiments, R^(8a) is

In some embodiments, R^(4b) is methoxy, R^(4c) is hydrogen, and R^(4d)is hydrogen.

In some embodiments, the metathesis catalyst is selected from the groupconsisting of:

In some embodiments, the metathesis catalyst is

In some embodiments, the metathesis catalyst is

In some embodiments, the metathesis catalyst is selected from:

wherein “Me” is methyl, “Ph” is phenyl, “i-Pr” is isopropyl, “Mes” ismesityl (i.e., 2,4,6-trimethylphenyl), and “TBS” istert-butyldimethylsilyl.

In some embodiments, the metathesis catalyst is

In some embodiments, the catalyst is a compound of Formula 3:

wherein:

-   -   each of R³¹ and R³² is independently R, —OR, —SR, —N(R)₂,        —OC(O)R, —SOR, —SO₂R, —SO₂N(R)₂, —C(O)N(R)₂, —NRC(O)R, or        —NRSO₂R;    -   each of R³³ and R³⁴ is independently halogen, R, —N(R)₂,        —NRC(O)R, —NRC(O)OR, —NRC(O)N(R)₂, —NRSO₂R, —NRSO₂N(R)₂, —NROR,        NR₃, —OR, a phosphorus-containing ligand, or an optionally        substituted group selected from:    -   a 5-6 membered monocyclic heteroaryl ring having at least one        nitrogen and 0-3 additional heteroatoms independently selected        from nitrogen, oxygen, or sulfur,    -   a 4-7 membered saturated or partially unsaturated heterocyclic        ring having at least one nitrogen and 0-2 additional heteroatoms        independently selected from nitrogen, oxygen, or sulfur,    -   a 7-10 membered bicyclic saturated or partially unsaturated        heterocyclic ring having at least one nitrogen and 0-4        additional heteroatoms independently selected from nitrogen,        oxygen, or sulfur, and    -   an 8-10 membered bicyclic heteroaryl ring having at least one        nitrogen and 0-4 additional heteroatoms independently selected        from nitrogen, oxygen, or sulfur;    -   each R is independently hydrogen or an optionally substituted        group selected from:    -   phenyl,    -   ferrocene,    -   C₁₋₂₀ aliphatic,    -   C₁₋₂₀ heteroaliphatic having 1-3 heteroatoms independently        selected from nitrogen, oxygen, or sulfur,    -   a 3-7 membered saturated or partially unsaturated carbocyclic        ring,    -   an 8-10 membered bicyclic saturated, partially unsaturated or        aryl ring,    -   a 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms        independently selected from nitrogen, oxygen, or sulfur,    -   a 4-7 membered saturated or partially unsaturated heterocyclic        ring having 1-3 heteroatoms independently selected from        nitrogen, oxygen, or sulfur,    -   a 7-10 membered bicyclic saturated or partially unsaturated        heterocyclic ring having 1-5 heteroatoms independently selected        from nitrogen, oxygen, or sulfur; and    -   an 8-10 membered bicyclic heteroaryl ring having 1-5 heteroatoms        independently selected from nitrogen, oxygen, or sulfur;    -   or two or three R groups on the same nitrogen atom are taken        together with the nitrogen to form an optionally substituted        3-12 membered saturated, partially unsaturated, or aryl ring        having 0-5 additional heteroatoms not including the same        nitrogen atom independently selected from nitrogen, oxygen, or        sulfur;    -   or two R groups on the same oxygen atom are taken together with        the oxygen to form an optionally substituted 3-12 membered        saturated, partially unsaturated, or aryl ring having 0-5        additional heteroatoms not including the same oxygen atom        independently selected from nitrogen, oxygen, or sulfur;    -   n is 0, 1, or 2;    -   each R³⁵ is independently a monodentate ligand, or two R³⁵ are        taken together with their intervening atoms to form an        optionally substituted bidentate group; and    -   two or more of R³¹, R³², R³³, R³⁴ and R³⁵ may be taken together        with their intervening atoms to form an optionally substituted        polydentate ligand.

In some embodiments, the metathesis catalyst has a structure accordingto Formula 3 and the metathesis product comprises a Z olefin.

In some embodiments, the catalyst is selected from:

W(O)(CH-t-Bu)(Ph₂Pyr)(OHMT); W(O)(CH-t-Bu)(Ph₂Pyr)(OHIPT); W(O)(CH-t-Bu)[N(C₆F₅)₂](OHMT)(PPhMe₂); W(O)(CH-t-Bu)(PMe₃)₂Cl₂;W(O)(CH-t-Bu)(O-2,6-Ph₂C₆H₃)₂(PMe₃); W(O)(CH-t-Bu)(C₁)(OHIPT);W(O)(CH-t-Bu)(PMe₂Ph)₂Cl₂; W(O) (CHCMe₂Ph)Cl₂(PMe₂Ph)₂;W[OB(C₆F₅)₃](CH-t-Bu)(Me₂Pyr)(OHMT); W(O)(CH-t-Bu)[N—(C₆F₅)₂](OHMT);W(O)(CH-t-Bu)(OHMT)₂; W(O)(CH-t-Bu)(OHIPT)₂;W(O)(CH-t-Bu)(Me₂Pyr)(DFTO)(PPhMe₂); W(O)(CH-t-Bu)(Me₂Pyr)(DFTO);W(O)(CHCMe₂Ph) (Me₂Pyr)(DFTO)(PPhMe₂); W(O)(CHCMe₂Ph)(Me₂Pyr)(DFTO);W(O)(CH-t-Bu)[N—(C₆F₅)₂](DFTO); and W(O)(CH-t-Bu)(DFTO)₂; wherein OHMTis O-2,6-dimesitylphenoxide; OHIPT isO-2,6-(2,4,6-triisopropylphenyl)₂C₆H₃; DFTO is2,6-pentafluorophenylphenoxide; Ph₂Pyr is 2,5-diphenylpyrrol-1-yl; andMe₂Pyr is 2,5-dimethylpyrrol-1-yl.

Other metathesis catalysts can be used in the methods of the invention.In general, any metathesis catalyst stable under the reaction conditionsand nonreactive with the functional groups present on the reactant shownin Schemes 3 through 8 may be used with the present invention. Suchcatalysts are, for example, those described by Grubbs (Grubbs, R. H.,“Synthesis of large and small molecules using olefin metathesiscatalysts.” PMSE Prepr., 2012), herein incorporated by reference in itsentirety. Depending on the desired isomer of the olefin, a cis-selectivemetathesis catalyst may be used, for example one of those described byShahane et al. (Shahane, S., et al. ChemCatChem, 2013. 5(12): p.3436-3459), herein incorporated by reference in its entirety. Specificcatalysts 1-5 exhibiting cis-selectivity are shown below (Scheme 5) andhave been described previously (Khan, R. K., et al. J. Am. Chem. Soc.,2013. 135(28): p. 10258-61; Hartung, J. et al. J. Am. Chem. Soc., 2013.135(28): p. 10183-5.; Rosebrugh, L. E., et al. J. Am. Chem. Soc., 2013.135(4): p. 1276-9.; Marx, V. M., et al. J. Am. Chem. Soc., 2013. 135(1):p. 94-7.; Herbert, M. B., et al. Angew. Chem. Int. Ed. Engl., 2013.52(1): p. 310-4; Keitz, B. K., et al. J. Am. Chem. Soc., 2012. 134(4):p. 2040-3.; Keitz, B. K., et al. J. Am. Chem. Soc., 2012. 134(1): p.693-9.; Endo, K. et al. J. Am. Chem. Soc., 2011. 133(22): p. 8525-7).

Additional Z-selective catalysts are described in (Cannon and Grubbs2013; Bronner et al. 2014; Hartung et al. 2014; Pribisko et al. 2014;Quigley and Grubbs 2014) and are herein incorporated by reference intheir entirety. Such metathesis catalysts include, but are not limitedto, neutral ruthenium or osmium metal carbene complexes that possessmetal centers that are formally in the +2 oxidation state, have anelectron count of 16, are penta-coordinated, and are of the generalformula LL′AA′M=CRbRc or LL′AA′M=(C═)nCRbRc (Pederson and Grubbs 2002);wherein

-   -   M is ruthenium or osmium;    -   L and L′ are each independently any neutral electron donor        ligand and preferably selected from phosphine, sulfonated        phosphine, phosphite, phosphinite, phosphonite, arsine,        stibnite, ether, amine, amide, imine, sulfoxide, carboxyl,        nitrosyl, pyridine, thioether, or heterocyclic carbenes; and    -   A and A′ are anionic ligands independently selected from        halogen, hydrogen, C₁-C₂₀ alkyl, aryl, C₁-C₂₀ alkoxide,        aryloxide, C₂-C₂₀ alkoxycarbonyl, arylcarboxylate, C₁-C₂₀        carboxylate, arylsulfonyl, C₁-C₂₀ alkylsulfonyl, C₁-C₂₀        alkylsulfinyl; each ligand optionally being substituted with        C₁-C₅ alkyl, halogen, C₁-C₅ alkoxy; or with a phenyl group that        is optionally substituted with halogen, C₁-C₅ alkyl, or C₁-C₅        alkoxy; and A and A′ together may optionally comprise a        bidentate ligand; and    -   R_(b) and R_(c) are independently selected from hydrogen, C₁-C₂₀        alkyl, aryl, C₁-C₂₀ carboxylate, C₁-C₂₀ alkoxy, aryloxy, C₁-C₂₀        alkoxycarbonyl, C₁-C₂₀ alkylthio, C₁-C₂₀ alkylsulfonyl and        C₁-C₂₀ alkylsulfinyl, each of R_(b) and R_(c) optionally        substituted with C₁-C₅ alkyl, halogen, C₁-C₅ alkoxy or with a        phenyl group that is optionally substituted with halogen, C₁-C₅        alkyl, or C₁-C₅ alkoxy.

Other metathesis catalysts such as “well defined catalysts” can also beused. Such catalysts include, but are not limited to, Schrock'smolybdenum metathesis catalyst, 2,6-diisopropylphenylimidoneophylidenemolybdenum (VI) bis(hexafluoro-t-butoxide), described byGrubbs et al. (Tetrahedron 1998, 54: 4413-4450) and Basset's tungstenmetathesis catalyst described by Couturier, J. L. et al. (Angew. Chem.Int. Ed. Engl. 1992, 31: 628).

Catalysts useful in the methods of the invention also include thosedescribed by Peryshkov, et al. J. Am. Chem. Soc. 2011, 133: 20754-20757;Wang, et al. Angewandte Chemie, 2013, 52: 1939-1943; Yu, et al. J. Am.Chem. Soc., 2012, 134: 2788-2799; Halford. Chem. Eng. News, 2011, 89(45): 11; Yu, et al. Nature, 2011, 479: 88-93; Lee. Nature, 2011, 471:452-453; Meek, et al. Nature, 2011: 471, 461-466; Flook, et al. J. Am.Chem. Soc. 2011, 133: 1784-1786; Zhao, et al. Org Lett., 2011, 13(4):784-787; Ondi, et al. “High activity, stabilized formulations, efficientsynthesis and industrial use of Mo- and W-based metathesis catalysts”XiMo Technology Updates, 2015:http://www.ximo-inc.com/files/ximo/uploads/download/Summary_3.11.15.pdf; Schrock, et al. Macromolecules, 2010: 43, 7515-7522; Peryshkov, etal. Organometallics 2013: 32, 5256-5259; Gerber, et al. Organometallics2013: 32, 5573-5580; Marinescu, et al. Organometallics 2012: 31,6336-6343; Wang, et al. Angew. Chem. Int. Ed. 2013: 52, 1939-1943; Wang,et al. Chem. Eur. J. 2013: 19, 2726-2740; Townsend et al. J. Am. Chem.Soc. 2012: 134, 11334-11337; and Johns et al. Org. Lett. 2016: 18,772-775.

Catalysts useful in the methods of the invention also include thosedescribed in International Pub. No. WO 2014/155185; International Pub.No. WO 2014/172534; U.S. Pat. Appl. Pub. No. 2014/0330018; InternationalPub. No. WO 2015/003815; and International Pub. No. WO 2015/003814.

Catalysts useful in the methods of the invention also include thosedescribed in U.S. Pat. Nos. 4,231,947; 4,245,131; 4,427,595; 4,681,956;4,727,215; International Pub. No. WO 1991/009825; U.S. Pat. Nos.5,087,710; 5,142,073; 5,146,033; International Pub. No. WO 1992/019631;U.S. Pat. Nos. 6,121,473; 6,346,652; 8,987,531; U.S. Pat. Appl. Pub. No.2008/0119678; International Pub. No. WO 2008/066754; International Pub.No. WO 2009/094201; U.S. Pat. Appl. Pub. No. 2011/0015430; U.S. Pat.Appl. Pub. No. 2011/0065915; U.S. Pat. Appl. Pub. No. 2011/0077421;International Pub. No. WO 2011/040963; International Pub. No. WO2011/097642; U.S. Pat. Appl. Pub. No. 2011/0237815; U.S. Pat. Appl. Pub.No. 2012/0302710; International Pub. No. WO 2012/167171; U.S. Pat. Appl.Pub. No. 2012/0323000; U.S. Pat. Appl. Pub. No. 2013/0116434;International Pub. No. WO 2013/070725; U.S. Pat. Appl. Pub. No.2013/0274482; U.S. Pat. Appl. Pub. No. 2013/0281706; International Pub.No. WO 2014/139679; International Pub. No. WO 2014/169014; U.S. Pat.Appl. Pub. No. 2014/0330018; and U.S. Pat. Appl. Pub. No. 2014/0378637.

Catalysts useful in the methods of the invention also include thosedescribed in International Pub. No. WO 2007/075427; U.S. Pat. Appl. Pub.No. 2007/0282148; International Pub. No. WO 2009/126831; InternationalPub. No. WO 2011/069134; U.S. Pat. Appl. Pub. No. 2012/0123133; U.S.Pat. Appl. Pub. No. 2013/0261312; U.S. Pat. Appl. Pub. No. 2013/0296511;International Pub. No. WO 2014/134333; and U.S. Pat. Appl. Pub. No.2015/0018557.

Catalysts useful in the methods of the invention also include those setforth in the following table:

Structure Name

dichloro[1,3-bis(2,6-isopropylphenyl)-2-imidazolidinylidene](benzylidene) (tricyclohexylphosphine)ruthenium(II)

dichloro[1,3-bis(2,6-isopropylphenyl)-2- imidazolidinylidene](2-isopropoxyphenylmethylene)ruthenium(II)

dichloro[1,3-Bis(2-methylphenyl)-2- imidazolidinylidene](benzylidene)(tricyclohexylphosphine)ruthenium(II)

dichloro[1,3-bis(2-methylphenyl)-2- imidazolidinylidene](2-isopropoxyphenylmethylene]ruthenium(II)

dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](benzylidene)bis(3- bromopyridine)ruthenium(II)

dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene](3-methyl-2- butenylidene) (tricyclohexylphosphine)ruthenium(II)

dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][3-(2-pyridinyl) propylidene]ruthenium(II)

dichloro[1,3-bis(2,4,6-trimethylphenyl)-2-imidazolidinylidene][(tricyclohexyl-phosphoranyl)methylidene]ruthenium(II) tetrafluoroborate

dichloro(3-methyl-2-butenylidene)bis(tricyclohexylphosphine)ruthenium(II)

dichloro(3-methyl-2-butenylidene)bis(tricyclopentylphosphine)ruthenium(II)

dichloro(tricyclohexylphosphine)[(tricyclo-hexylphosphoranyl)methylidene] ruthenium(II)tetrafluoroborate

bis(tricyclohexylphosphine) benzylidine ruthenium(IV) dichloride

[1,3-bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene]dichloro(phenylmethylene)(tricyclohexylphosphine)ruthenium

(1,3-bis-(2,4,6-trimethylphenyl)-2- imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium

dichloro(o-isopropoxyphenylmethylene)(tricyclohexylphosphine)ruthenium(II)

[2-(1-methylethoxy-O)phenylmethyl-C](nitrato-O,O′){rel-(2R,5R,7R)-adamantane-2,1-diyl[3-(2,4,6-trimethylphenyl)-1-imidazolidinyl-2-ylidene]}ruthenium

In some embodiments, the metathesis product comprises an E olefin, andthe metathesis catalyst is selected from the group consisting of:

In some embodiments, the metathesis product comprises an E olefin, andthe metathesis catalyst is selected from the group consisting of:

In some embodiments, the metathesis product comprises an E olefin, andthe metathesis catalyst is selected from the group consisting of:

Catalysts useful in the methods of the invention also include thosedescribed in U.S. Pat. Appl. Pub. No. 2008/0009598; U.S. Pat. Appl. Pub.No. 2008/0207911; U.S. Pat. Appl. Pub. No. 2008/0275247; U.S. Pat. Appl.Pub. No. 2011/0040099; U.S. Pat. Appl. Pub. No. 2011/0282068; and U.S.Pat. Appl. Pub. No. 2015/0038723.

Catalysts useful in the methods of the invention include those describedin International Pub. No. WO 2007/140954; U.S. Pat. Appl. Pub. No.2008/0221345; International Pub. No. WO 2010/037550; U.S. Pat. Appl.Pub. No. 2010/0087644; U.S. Pat. Appl. Pub. No. 2010/0113795; U.S. Pat.Appl. Pub. No. 2010/0174068; International Pub. No. WO 2011/091980;International Pub. No. WO 2012/168183; U.S. Pat. Appl. Pub. No.2013/0079515; U.S. Pat. Appl. Pub. No. 2013/0144060; U.S. Pat. Appl.Pub. No. 2013/0211096; International Pub. No. WO 2013/135776;International Pub. No. WO 2014/001291; International Pub. No. WO2014/067767; U.S. Pat. Appl. Pub. No. 2014/0171607; and U.S. Pat. Appl.Pub. No. 2015/0045558.

Metathesis Reaction Conditions

The catalyst is typically provided in the reaction mixture in asub-stoichiometric amount (e.g., catalytic amount). In certainembodiments, that amount is in the range of about 0.001 to about 50 mol% with respect to the limiting reagent of the chemical reaction,depending upon which reagent is in stoichiometric excess. In someembodiments, the catalyst is present in less than or equal to about 40mol % relative to the limiting reagent. In some embodiments, thecatalyst is present in less than or equal to about 30 mol % relative tothe limiting reagent. In some embodiments, the catalyst is present inless than about 20 mol %, less than about 10 mol %, less than about 5mol %, less than about 2.5 mol %, less than about 1 mol %, less thanabout 0.5 mol %, less than about 0.1 mol %, less than about 0.015 mol %,less than about 0.01 mol %, less than about 0.0015 mol %, or less,relative to the limiting reagent. In some embodiments, the catalyst ispresent in the range of about 2.5 mol % to about 5 mol %, relative tothe limiting reagent. In some embodiments, the reaction mixture containsabout 0.5 mol % catalyst. In the case where the molecular formula of thecatalyst complex includes more than one metal, the amount of thecatalyst complex used in the reaction may be adjusted accordingly.

In some cases, the methods described herein can be performed in theabsence of solvent (e.g., neat). In some cases, the methods can includethe use of one or more solvents. Examples of solvents that may besuitable for use in the invention include, but are not limited to,benzene, p-cresol, toluene, xylene, diethyl ether, glycol, diethylether, petroleum ether, hexane, cyclohexane, pentane, methylenechloride, chloroform, carbon tetrachloride, dioxane, tetrahydrofuran(THF), dimethyl sulfoxide, dimethylformamide, hexamethyl-phosphorictriamide, ethyl acetate, pyridine, triethylamine, picoline, and thelike, as well as mixtures thereof. In some embodiments, the solvent isselected from benzene, toluene, pentane, methylene chloride, and THF. Incertain embodiments, the solvent is benzene.

In some embodiments, the method is performed under reduced pressure.This may be advantageous in cases where a volatile byproduct, such asethylene, may be produced during the course of the metathesis reaction.For example, removal of the ethylene byproduct from the reaction vesselmay advantageously shift the equilibrium of the metathesis reactiontowards formation of the desired product. In some embodiments, themethod is performed at a pressure of about less than 760 torr. In someembodiments, the method is performed at a pressure of about less than700 torr. In some embodiments, the method is performed at a pressure ofabout less than 650 torr. In some embodiments, the method is performedat a pressure of about less than 600 torr. In some embodiments, themethod is performed at a pressure of about less than 550 torr. In someembodiments, the method is performed at a pressure of about less than500 torr. In some embodiments, the method is performed at a pressure ofabout less than 450 torr. In some embodiments, the method is performedat a pressure of about less than 400 torr. In some embodiments, themethod is performed at a pressure of about less than 350 torr. In someembodiments, the method is performed at a pressure of about less than300 torr. In some embodiments, the method is performed at a pressure ofabout less than 250 torr. In some embodiments, the method is performedat a pressure of about less than 200 torr. In some embodiments, themethod is performed at a pressure of about less than 150 torr. In someembodiments, the method is performed at a pressure of about less than100 torr. In some embodiments, the method is performed at a pressure ofabout less than 90 torr. In some embodiments, the method is performed ata pressure of about less than 80 torr. In some embodiments, the methodis performed at a pressure of about less than 70 torr. In someembodiments, the method is performed at a pressure of about less than 60torr. In some embodiments, the method is performed at a pressure ofabout less than 50 torr. In some embodiments, the method is performed ata pressure of about less than 40 torr. In some embodiments, the methodis performed at a pressure of about less than 30 torr. In someembodiments, the method is performed at a pressure of about less than 20torr. In some embodiments, the method is performed at a pressure ofabout 20 torr.

In some embodiments, the method is performed at a pressure of about 19torr. In some embodiments, the method is performed at a pressure ofabout 18 torr. In some embodiments, the method is performed at apressure of about 17 torr. In some embodiments, the method is performedat a pressure of about 16 torr. In some embodiments, the method isperformed at a pressure of about 15 torr. In some embodiments, themethod is performed at a pressure of about 14 torr. In some embodiments,the method is performed at a pressure of about 13 torr. In someembodiments, the method is performed at a pressure of about 12 torr. Insome embodiments, the method is performed at a pressure of about 11torr. In some embodiments, the method is performed at a pressure ofabout 10 torr. In some embodiments, the method is performed at apressure of about 10 torr. In some embodiments, the method is performedat a pressure of about 9 torr. In some embodiments, the method isperformed at a pressure of about 8 torr. In some embodiments, the methodis performed at a pressure of about 7 torr. In some embodiments, themethod is performed at a pressure of about 6 torr. In some embodiments,the method is performed at a pressure of about 5 torr. In someembodiments, the method is performed at a pressure of about 4 torr. Insome embodiments, the method is performed at a pressure of about 3 torr.In some embodiments, the method is performed at a pressure of about 2torr. In some embodiments, the method is performed at a pressure ofabout 1 torr. In some embodiments, the method is performed at a pressureof less than about 1 torr.

In some embodiments, the two metathesis reactants are present inequimolar amounts. In some embodiments, the two metathesis reactants arenot present in equimolar amounts. In certain embodiments, the tworeactants are present in a molar ratio of about 20:1, 19:1, 18:1, 17:1,16:1, 15:1, 14:1, 13:1, 12:1, 11:1, 10:1, 9:1, 8:1, 7:1, 6:1, 5:1, 4:1,3:1, 2:1, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, 1:11, 1:12,1:13, 1:14, 1:15, 1:16, 1:17, 1:18, 1:19, or 1:20. In certainembodiments, the two reactants are present in a molar ratio of about10:1. In certain embodiments, the two reactants are present in a molarratio of about 7:1. In certain embodiments, the two reactants arepresent in a molar ratio of about 5:1. In certain embodiments, the tworeactants are present in a molar ratio of about 2:1. In certainembodiments, the two reactants are present in a molar ratio of about1:10. In certain embodiments, the two reactants are present in a molarratio of about 1:7. In certain embodiments, the two reactants arepresent in a molar ratio of about 1:5. In certain embodiments, the tworeactants are present in a molar ratio of 1:2.

In some embodiments, one molar equivalent of the olefin is contactedwith one molar equivalent of the metathesis reaction partner. In someembodiments, about 1.5, 2, 2.5, or 3 molar equivalents of the olefin iscontacted with one molar equivalent of the metathesis reaction partner.In some embodiments, about 1.5 molar equivalents of the olefin iscontacted with one molar equivalent of the metathesis reaction partner.

In general, the reactions with many of the metathesis catalystsdisclosed herein provide yields better than 15%, e.g., better than 50%,better than 75%, or better than 90%. In addition, the reactants andproducts are chosen to provide at least a 5° C. difference, e.g., agreater than 20° C. difference, or a greater than 40° C. difference inboiling points. Additionally, the use of metathesis catalysts allows formuch faster product formation than byproduct, and it can be desirable torun these reactions as quickly as practical. In particular, thereactions are performed in less than about 24 hours, e.g., less than 12hours, or less than 8 hours, or less than 4 hours. Advantageously, themethods of the invention provide metathesis products on a scale rangingfrom a few milligrams to hundreds of kilograms or more. For example, themethods can be conducted using around 1-10 grams of the olefin accordingto Formula I, or around 10-100 grams of the olefin according to FormulaI, or around 100-500 grams of the olefin according to Formula I, oraround 500-1000 grams of the olefin according to Formula I. The methodscan be conducted using at least 1, 5, 10, 25, 50, 100, or 1,000kilograms of starting material. The metathesis reactions can beconducted using a metathesis reactor as described, for example, in WO2011/046872, which reactor can be operated in conjuction with one ormore downstream separation units for separating and/or recyclingparticular product or byproduct streams (e.g., an olefin stream, a C₂-C₃compound stream, or a C₃-C₅ compound stream). The metathesis reactor andseparation unit(s) can be operated in conjunction with one or moreadsorbent beds to facilitate the separation of the metathesized productsfrom the catalyst, as well as washing and drying units for purificationof desired products. The metathesis, reduction, and acylation reactionscan be conducted to provide products on the scale of metric tons.

One of skill in the art will appreciate that the time, temperature andsolvent can depend on each other, and that changing one can requirechanging the others to prepare the metathesis products in the methods ofthe invention. The metathesis steps can proceed at a variety oftemperatures and times. In general, reactions in the methods of theinvention are conducted using reaction times of several minutes toseveral days. For example, reaction times of from about 12 hours toabout 7 days can be used. In some embodiments, reaction times of 1-5days can be used. In some embodiments, reaction times of from about 10minutes to about 10 hours can be used. In general, reactions in themethods of the invention are conducted at a temperature of from about 0°C. to about 200° C. For example, reactions can be conducted at 15-100°C. In some embodiments, reaction can be conducted at 20-80° C. In someembodiments, reactions can be conducted at 100-150° C.

The olefins, fatty alcohols, fatty acid esters, and other materials usedin the methods of the invention can be obtained from any suitablesource. In some embodiments, the metathesis reaction partners used inthe methods of the invention are obtained from a natural oil and/or aderivative thereof. Representative examples of natural oils for use inaccordance with the present teachings include but are not limited tovegetable oils, algal oils, animal fats, tall oils (e.g., by-products ofwood pulp manufacture), derivatives of these oils, and the like, andcombinations thereof. Representative examples of vegetable oils for usein accordance with the present teachings include but are not limited tocanola oil, rapeseed oil, coconut oil, corn oil, cottonseed oil, oliveoil, palm oil, peanut oil, safflower oil, sesame oil, soybean oil,sunflower oil, high oleic sunflower oil, linseed oil, palm kernel oil,tung oil, jatropha oil, jojoba oil, mustard oil, pennycress oil,camelina oil, hemp oil, castor oil, and the like, and combinationsthereof. Representative examples of animal fats for use in accordancewith the present teachings include but are not limited to lard, tallow,poultry fat, yellow grease, brown grease, fish oil, and the like, andcombinations thereof. The natural oil can be refined, bleached, and/ordeodorized.

Representative examples of natural oil derivatives for use in accordancewith the method of the invention include, but are not limited to, gums,phospholipids, soapstock, acidulated soapstock, distillate or distillatesludge, fatty acids, fatty acid esters (e.g., non-limiting examples suchas 2-ethylhexyl ester, etc.), hydroxy-substituted variations thereof,and the like, and combinations thereof. In some embodiments, the naturaloil derivative comprises an ester. In some embodiments, the derivativeis selected from the group consisting of a monoacylglyceride (MAG), adiacylglyceride (DAG), a triacylglyceride (TAG), and combinationsthereof. In some embodiments, the natural oil derivative comprises afatty acid methyl ester (FAME) derived from the glyceride of the naturaloil.

In some embodiments, a feedstock includes canola or soybean oil, e.g.,refined, bleached, and/or deodorized soybean oil (i.e., RBD soybeanoil). Soybean oil typically contains about 95% weight or greater (e.g.,99% weight or greater) triglycerides of fatty acids. Major fatty acidsin the polyol esters of soybean oil include saturated fatty acids,including palmitic acid (hexadecanoic acid) and stearic acid(octadecanoic acid), and unsaturated fatty acids, including oleic acid(9-octadecenoic acid), linoleic acid (9, 12-octadecadienoic acid), andlinolenic acid (9, 12, 15-octadecatrienoic acid).

In some embodiments, materials to be reacted in a metathesisreaction—including those derived from natural oils—will containing oneor more contaminants with the potential to adversely affect theperformance of a metathesis catalyst. Such contaminants can be referredto as “catalyst poisons” or “catalyst poisoning contaminants.” Thecontaminant levels can be reduced according to the methods describedherein. In some embodiments, the material comprises a plurality ofcontaminants and the method comprises reducing levels of two or more ofthe contaminants. In some embodiments, the material comprises aplurality of contaminants and the method comprises reducing levels ofthree or more of the contaminants. In some embodiments, the materialcomprises a plurality of contaminants and the method comprises reducinglevels of four or more of the contaminants. In some embodiments, thematerial comprises a plurality of contaminants and the method comprisesreducing levels of five or more of the contaminants.

Representative contaminants include but are not limited to water,peroxides, peroxide decomposition products, hydroperoxides, proticmaterials, polar materials, Lewis basic catalyst poisons, and the like,and combinations thereof. It is to be understood that some contaminantsmay properly be classified in multiple categories (e.g., an alcohol canbe considered both a protic material and a polar material). It is to befurther understood that different catalysts may have differentsusceptibilities to a particular contaminant, and that a contaminantthat adversely affects the performance of one catalyst (e.g., aruthenium-based catalyst) may or may not affect (to a similar extent orto any extent whatsoever) a different catalyst (e.g., a molybdenum-basedcatalyst).

Representative protic materials that may be found as contaminants in asubstrate that is to be reacted in a metathesis reaction include but arenot limited to materials having a hydrogen atom bonded to oxygen (e.g.,carboxylic acids, alcohols, and the like) and/or a hydrogen atom bondedto nitrogen (e.g., primary amines, secondary amines, and the like). Insome embodiments, particularly though not exclusively in natural oilsubstrates, a protic material contaminant may comprise a carboxylic acidfunctional group, a hydroxyl functional group, or a combination thereof.In some embodiments, the protic material is selected from the groupconsisting of free fatty acids, hydroxyl-containing materials, MAGs,DAGs, and the like, and combinations thereof.

Representative polar materials that may be found as contaminants in asubstrate that is to be reacted in a metathesis reaction include but arenot limited to heteroatom-containing materials such as oxygenates. Insome embodiments, the polar material is selected from the groupconsisting of alcohols, aldehydes, ethers, and the like, andcombinations thereof.

Representative Lewis basic catalyst poisons that may be found ascontaminants in a substrate that is to be reacted in a metathesisreaction include but are not limited to heteroatom-containing materials.In some embodiments, the Lewis basic catalyst poisons are selected fromthe group consisting of N-containing materials, P-containing materials,S-containing materials, and the like, and combinations thereof.

Reaction materials containing contaminants can be treated with one ormore conditioning agents that mitigate potentially adverse effects ofone or more of the contaminants. Conditioning agents that can be used inthe methods of the invention (individually, or in combinationsequentially or simultaneously) include heat, molecular sieves, alumina(aluminum oxide), silica gel, montmorillonite clay, fuller's earth,bleaching clay, diatomaceous earth, zeolites, kaolin, activated metals(e.g., Cu, Mg, and the like), acid anhydrides (e.g., acetic anhydrideand the like), activated carbon (i.e., activated charcoal), soda ash,metal hydrides (e.g., alkaline earth metal hydrides such as CaH₂ and thelike), metal sulfates (e.g., alkaline earth metal sulfates such ascalcium sulfate, magnesium sulfate, and the like; alkali metal sulfatessuch as potassium sulfate, sodium sulfate, and the like; and other metalsulfates such as aluminum sulfate, potassium magnesium sulfate, and thelike), metal halides (e.g., alkali earth metal halides such as potassiumchloride and the like), metal carbonates (e.g., calcium carbonate,sodium carbonate, and the like), metal silicates (e.g., magnesiumsilicate and the like), phosphorous pentoxide, metal aluminum hydrides(e.g., alkali metal aluminum hydrides such as LiAlH₄, NaAlH₄, and thelike), alkyl aluminum hydrides (e.g., DIBALH), metal borohydrides (e.g.,alkali metal borohydrides such as LiBH₄, NaBH₄, and the like),organometallic reagents (e.g., Grignard reagents; organolithium reagentssuch as n-butyl lithium, t-butyl lithium, sec-butyl lithium; trialkylaluminums such as triethyl aluminum, tributyl aluminum, triisobutylaluminum, triisopropyl aluminum, trioctyl aluminum, and the like, metalamides (e.g., lithium diisopropyl amide, metal bis(trimethylsilyl)amidessuch as KHMDS, and the like), palladium on carbon (Pd/C) catalysts, andcombinations thereof.

In some embodiments, the conditioning agent is a metal alkyl compound.In some embodiments, the metal, M, can be lithium, sodium, potassium,magnesium, calcium, zinc, cadmium, aluminum, or gallium. Examples ofsuitable alkyl radicals, R, include, but are not limited to, methyl,ethyl, butyl, hexyl, decyl, tetradecyl, and eicosyl. Examples of metalalkyl compounds include, but are not limited to, Mg(CH₃)₂, Mg(C₂H₅)₂,Mg(C₂H₅)(C₄H₉), Mg(C₄H₉)₂, Mg(C₆H₁₃)₂, Mg(Cl₂H₂₅)₂, Zn(CH₃)₂, Zn(C₂H₅)₂,Zn(C₄H₉)₂, Zn(C₄H₉)(C₈H₁₇), Zn(C₆H₁₃)₂, Zn(C₆H₃)₂, Al(C₂H₅)₃, Al(CH₃)₃,Al(n-C₄H₉)₃, Al(C₈H₁₇)₃, Al(iso-C₄H₉)₃, Al(Cl₂H₂₅)₃, and combinationsthereof. Metal alkyl compounds also include substances having one ormore halogen or hydride groups, such as ethylaluminum dichloride,diethylaluminum chloride, diethylaluminum hydride, Grignard reagents,diisobutylaluminum hydride, and the like.

In some embodiments, the treating of the metathesis reaction material(e.g., a natural oil or a natural oil derivative) can include contactingthe reaction material with a metal alkyl compound and, eithersimultaneously or separately, contacting the reaction material with ahydride-containing compound. In some embodiments, where the reactionmaterial is contacted simultaneously with the metal alkyl compound andthe hydride-containing compound, the hydride-containing compounds can beincluded in the metal alkyl compound. For example, in some instances,processes used to make certain metal alkyl compounds, such as trialkylaluminum compounds, can lead to the formation of a certain concentrationof hydride-containing compounds. In other embodiments, however, themetal alkyl compounds can be combined with one or morehydride-containing compounds. Or, in some embodiments, the metathesisreaction material can be treated by the hydride-containing compounds ina separate treatment step, which can be performed before, after, or bothbefore and after, treatment of the reaction material with the metalalkyl compounds.

Any suitable hydride-containing compounds can be used. In someembodiments, the hydride-containing compounds are selected from thegroup consisting of metal aluminum hydrides (e.g., alkali metal aluminumhydrides such as LiAlH₄, NaAlH₄, and the like), alkyl aluminum hydrides(e.g., DIBALH), and combinations thereof. In some embodiments, thehydride-containing compound is an alkyl aluminum hydride, such asDIBALH.

In some embodiments, contacting the metathesis reaction material withthe hydride-containing compound occurs in the same step as contactingthe reaction material with the metal alkyl compound. In someembodiments, the weight-to-weight ratio of the metal alkyl compound tothe hydride-containing compound in the treatment composition is from2:1, or from 5:1, or from 10:1, or from 15:1, or from 20:1 to 1000:1. Insome embodiments, the weight-to-weight ratio of the metal alkyl compoundto the hydride-containing compound in the treatment composition is atleast 2:1, or at least 5:1, or at least 10:1, or at least 15:1, or atleast 20:1.

In certain instances, the efficacy of the metathesis catalyst can beimproved (e.g., the turnover number can be increased or the overallcatalyst loading may be decreased) through slow addition of the catalystto a substrate. The overall catalyst loading can be decreased by atleast 10%, at least 20%, or at least 30% when administered slowly toachieve the same turnover number as a single, full batch loading. Theslow addition of overall catalyst loading can include adding fractionalcatalyst loadings to the reaction materials at an average rate ofapproximately 10 ppm by weight of catalyst per hour (ppmwt/hr), 5ppmwt/hr, 1 ppmwt/hr, 0.5 ppmwt/hr, 0.1 ppmwt/hr, 0.05 ppmwt/hr, or 0.01ppmwt/hr. In some embodiments, the catalyst is slowly added at a rate ofbetween about 0.01-10 ppmwt/hr, 0.05-5 ppmwt/hr, or 0.1-1 ppmwt/hr. Theslow addition of the catalyst can be conducted in batch loadings atfrequencies of every 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours,4 hours, 12 hours, or 1 day. In other embodiments, the slow addition isconducted in a continuous addition process.

Pheromone Products

As described above, a number of the fatty olefin derivatives obtainedvia the methods of the invention can be used as insect pheromones orpheromone precursor materials. The precursor materials and pheromoneproducts include, for example, the compounds listed in Table 1 and Table6. The method can be used for synthesizing one or more of the pheromoneslisted in Table 7.

TABLE 7 Pheromone products. Name Name Name (E)-2-Decen-1-ol(Z,Z)-5,9-Tridecadienyl (Z)-10-Hexadecenal acetate (E)-2-Decenyl acetate(Z,Z)-7,11-Tridecadienyl (E)-11-Hexadecen-1-ol acetate (E)-2-Decenal(E,Z,Z)-4,7,10-Tridecatrienyl (E)-11-Hexadecenyl acetate acetate(Z)-2-Decen-1-ol (E)-3-Tetradecen-1-ol (E)-11-Hexadecenal (Z)-2-Decenylacetate (E)-3-Tetradecenyl acetate (Z)-11-Hexadecen-1-ol (Z)-2-Decenal(Z)-3-Tetradecen-1-ol (Z)-11-Hexadecenyl acetate (E)-3-Decen-1-ol(Z)-3-Tetradecenyl acetate (Z)-11-Hexadecenal (Z)-3-Decenyl acetate(E)-5-Tetradecen-1-ol (Z)-12-Hexadecenyl acetate (Z)-3-Decen-1-ol(E)-5-Tetradecenyl acetate (Z)-12-Hexadecenal (Z)-4-Decen-1-ol(E)-5-Tetradecenal (E)-14-Hexadecenal (E)-4-Decenyl acetate(Z)-5-Tetradecen-1-ol (Z)-14-Hexadecenyl acetate (Z)-4-Decenyl acetate(Z)-5-Tetradecenyl acetate (E,E)-1,3-Hexadecadien-1-ol (Z)-4-Decenal(Z)-5-Tetradecenal (E,Z)-4,6-Hexadecadien-1-ol (E)-5-Decen-1-ol(E)-6-Tetradecenyl acetate (E,Z)-4,6-Hexadecadienyl acetate(E)-5-Decenyl acetate (Z)-6-Tetradecenyl acetate(E,Z)-4,6-Hexadecadienal (Z)-5-Decen-1-ol (E)-7-Tetradecen-1-ol(E,Z)-6,11-Hexadecadienyl acetate (Z)-5-Decenyl acetate(E)-7-Tetradecenyl acetate (E,Z)-6,11-Hexadecadienal (Z)-5-Decenal(Z)-7-Tetradecen-1-ol (Z,Z)-7,10-Hexadecadien-1-ol (E)-7-Decenyl acetate(Z)-7-Tetradecenyl acetate (Z,Z)-7,10-Hexadecadienyl acetate(Z)-7-Decenyl acetate (Z)-7-Tetradecenal (Z,E)-7,11-Hexadecadien-1-ol(E)-8-Decen-1-ol (E)-8-Tetradecenyl acetate (Z,E)-7,11-Hexadecadienylacetate (E,E)-2,4-Decadienal (Z)-8-Tetradecen-1-ol(Z,E)-7,11-Hexadecadienal (E,Z)-2,4-Decadienal (Z)-8-Tetradecenylacetate (Z,Z)-7,11-Hexadecadien-1-ol (Z,Z)-2,4-Decadienal(Z)-8-Tetradecenal (Z,Z)-7,11-Hexadecadienyl acetate (E,E)-3,5-Decadienyl (E)-9-Tetradecen-1-ol (Z,Z)-7,11-Hexadecadienal acetate(Z,E)-3,5-Decadienyl (E)-9-Tetradecenyl acetate(Z,Z)-8,10-Hexadecadienyl acetate acetate (Z,Z)-4,7-Decadien-1-ol(Z)-9-Tetradecen-1-ol (E,Z)-8,11-Hexadecadienal (Z,Z)-4,7-Decadienyl(Z)-9-Tetradecenyl acetate (E,E)-9,11-Hexadecadienal acetate(E)-2-Undecenyl acetate (Z)-9-Tetradecenal (E,Z)-9,11-Hexadecadienylacetate (E)-2-Undecenal (E)-10-Tetradecenyl (E,Z)-9,11-Hexadecadienalacetate (Z)-5-Undecenyl acetate (Z)-10-Tetradecenyl(Z,E)-9,11-Hexadecadienal acetate (Z)-7-Undecenyl acetate(E)-11-Tetradecen-1-ol (Z,Z)-9,11-Hexadecadienal (Z)-8-Undecenyl acetate(E)-11-Tetradecenyl (E,E)-10,12-Hexadecadien-1-ol acetate(Z)-9-Undecenyl acetate (E)-11-Tetradecenal (E,E)-10,12-Hexadecadienylacetate (E)-2-Dodecenal (Z)-11-Tetradecen-1-ol(E,E)-10,12-Hexadecadienal (Z)-3-Dodecen-1-ol (Z)-11-Tetradecenyl(E,Z)-10,12-Hexadecadien-1-ol acetate (E)-3-Dodecenyl acetate(Z)-11-Tetradecenal (E,Z)-10,12-Hexadecadienyl acetate (Z)-3-Dodecenylacetate (E)-12-Tetradecenyl (E,Z)-10,12-Hexadecadienal acetate(E)-4-Dodecenyl acetate (Z)-12-Tetradecenyl (Z,E)-10,12-Hexadecadienylacetate acetate (E)-5-Dodecen-1-ol (E,E)-2,4-Tetradecadienal(Z,E)-10,12-Hexadecadienal (E)-5-Dodecenyl acetate(E,E)-3,5-Tetradecadienyl (Z,Z)-10,12-Hexadecadienal acetate(Z)-5-Dodecen-1-ol (E,Z)-3,5-Tetradecadienyl(E,E)-11,13-Hexadecadien-1-ol acetate (Z)-5-Dodecenyl acetate(Z,E)-3,5-Tetradecadienyl (E,E)-11,13-Hexadecadienyl acetate acetate(Z)-5-Dodecenal (E,Z)-3,7-Tetradecadienyl (E,E)-11,13-Hexadecadienalacetate (E)-6-Dodecen-1-ol (E,Z)-3,8-Tetradecadienyl(E,Z)-11,13-Hexadecadien-1-ol acetate (Z)-6-Dodecenyl acetate(E,Z)-4,9-Tetradecadienyl (E,Z)-11,13-Hexadecadienyl acetate acetate(E)-6-Dodecenal (E,Z)-4,9-Tetradecadienal (E,Z)-11,13-Hexadecadienal(E)-7-Dodecen-1-ol (E,Z)-4,10-Tetradecadienyl(Z,E)-11,13-Hexadecadien-1-ol acetate (E)-7-Dodecenyl acetate(E,E)-5,8-Tetradecadienal (Z,E)-11,13-Hexadecadienyl acetate(E)-7-Dodecenal (Z,Z)-5,8-Tetradecadien-1-ol (Z,E)-11,13-Hexadecadienal(Z)-7-Dodecen-1-ol (Z,Z)-5,8-Tetradecadienyl(Z,Z)-11,13-Hexadecadien-1-ol acetate (Z)-7-Dodecenyl acetate(Z,Z)-5,8-Tetradecadienal (Z,Z)-11,13-Hexadecadienyl acetate(Z)-7-Dodecenal (E,E)-8,10-Tetradecadien-1-ol (Z,Z)-11,13-Hexadecadienal(E)-8-Dodecen-1-ol (E,E)-8,10-Tetradecadienyl (E,E)-10,14-Hexadecadienalacetate (E)-8-Dodecenyl acetate (E,E)-8,10-Tetradecadienal(Z,E)-11,14-Hexadecadienyl acetate (E)-8-Dodecenal(E,Z)-8,10-Tetradecadienyl (E,E,Z)-4,6,10- acetate Hexadecatrien-1 -ol(Z)-8-Dodecen-1-ol (E,Z)-8,10-Tetradecadienal(E,E,Z)-4,6,10-Hexadecatrienyl acetate (Z)-8-Dodecenyl acetate(Z,E)-8,10-Tetradecadien-1-ol (E,Z,Z)-4,6,10-Hexadecatrien-1-ol(E)-9-Dodecen-1-ol (Z,E)-8,10-Tetradecadienyl(E,Z,Z)-4,6,10-Hexadecatrienyl acetate acetate (E)-9-Dodecenyl acetate(Z,Z)-8,10-Tetradecadienal (E,E,Z)-4,6,11-Hexadecatrienyl acetate(E)-9-Dodecenal (E,E)-9,11-Tetradecadienyl(E,E,Z)-4,6,11-Hexadecatrienal acetate (Z)-9-Dodecen-1-ol(E,Z)-9,11-Tetradecadienyl (Z,Z,E)-7,11,13-Hexadecatrienal acetate(Z)-9-Dodecenyl acetate (Z,E)-9,11-Tetradecadien-1-ol(E,E,E)-10,12,14-Hexadecatrienyl acetate (Z)-9-Dodecenal(Z,E)-9,11-Tetradecadienyl (E,E,E)-10,12,14-Hexadecatrienal acetate(E)-10-Dodecen-1-ol (Z,E)-9,11-Tetradecadienal (E,E,Z)-10,12,14-Hexadecatrienyl acetate (E)-10-Dodecenyl acetate(Z,Z)-9,11-Tetradecadien-1-ol (E, E,Z)-10,12,14- Hexadecatrienal(E)-10-Dodecenal (Z,Z)-9,11-Tetradecadienyl(E,E,Z,Z)-4,6,11,13-Hexadecatetraenal acetate (Z)-10-Dodecen-1-ol(Z,Z)-9,11-Tetradecadienal (E)-2-Heptadecenal (Z)-10-Dodecenyl acetate(E,E)-9,12-Tetradecadienyl (Z)-2-Heptadecenal acetate(E,Z)-3,5-Dodecadienyl (Z,E)-9,12-Tetradecadien-1-ol(E)-8-Heptadecen-1-ol acetate (Z,E)-3,5-Dodecadienyl(Z,E)-9,12-Tetradecadienyl (E)-8-Heptadecenyl acetate acetate acetate(Z,Z)-3,6-Dodecadien-1-ol (Z,E)-9,12-Tetradecadienal(Z)-8-Heptadecen-1-ol (E,E)-4,10-Dodecadienyl(Z,Z)-9,12-Tetradecadien-1-ol (Z)-9-Heptadecenal acetate(E,E)-5,7-Dodecadien-1-ol (Z,Z)-9,12-Tetradecadienyl (E)-10-Heptadecenylacetate acetate (E,E)-5,7-Dodecadienyl (E,E)-10,12-Tetradecadien-1-ol(Z)-11-Heptadecen-1-ol acetate (E,Z)-5,7-Dodecadien-1-ol(E,E)-10,12-Tetradecadienyl (Z)-11-Heptadecenyl acetate acetate(E,Z)-5,7-Dodecadienyl (E,E)-10,12-Tetradecadienal(E,E)-4,8-Heptadecadienyl acetate acetate (E,Z)-5,7-Dodecadienal(E,Z)-10,12-Tetradecadienyl (Z,Z)-8,10-Heptadecadien-1-ol acetate(Z,E)-5,7-Dodecadien-1-ol (Z,E)-10,12-Tetradecadienyl(Z,Z)-8,11-Heptadecadienyl acetate acetate (Z,E)-5,7-Dodecadienyl(Z,Z)-10,12-Tetradecadien-1-ol (E)-2-Octadecenyl acetate acetate(Z,E)-5,7-Dodecadienal (Z,Z)-10,12-Tetradecadienyl (E)-2-Octadecenalacetate (Z,Z)-5,7-Dodecadienyl (E,Z,Z)-3,8,11-Tetradecatrienyl(Z)-2-Octadecenyl acetate acetate acetate (Z,Z)-5,7-Dodecadienal(E)-8-Pentadecen-1-ol (Z)-2-Octadecenal (E,E)-7,9-Dodecadienyl(E)-8-Pentadecenyl acetate (E)-9-Octadecen-1-ol acetate(E,Z)-7,9-Dodecadien-1-ol (Z)-8-Pentadecen-1-ol (E)-9-Octadecenylacetate (E,Z)-7,9-Dodecadienyl (Z)-8-Pentadecenyl acetate(E)-9-Octadecenal acetate (E,Z)-7,9-Dodecadienal (Z)-9-Pentadecenylacetate (Z)-9-Octadecen-1-ol (Z,E)-7,9-Dodecadien-1-ol(E)-9-Pentadecenyl acetate (Z)-9-Octadecenyl acetate(Z,E)-7,9-Dodecadienyl (Z)-10-Pentadecenyl (Z)-9-Octadecenal acetateacetate (Z,Z)-7,9-Dodecadien-1-ol (Z)-10-Pentadecenal(E)-11-Octadecen-1-ol (Z,Z)-7,9-Dodecadienyl (E)-12-Pentadecenyl(E)-11-Octadecenal acetate acetate (E,E)-8,10-Dodecadien-1-ol(Z)-12-Pentadecenyl (Z)-11-Octadecen-1-ol acetate(E,E)-8,10-Dodecadienyl (Z,Z)-6,9-Pentadecadien-1-ol (Z)-11-Octadecenylacetate acetate (E,E)-8,10-Dodecadienal (Z,Z)-6,9-Pentadecadienyl(Z)-11-Octadecenal acetate (E,Z)-8,10-Dodecadien-1-ol(Z,Z)-6,9-Pentadecadienal (E)-13-Octadecenyl acetate(E,Z)-8,10-Dodecadienyl (E,E)-8,10-Pentadecadienyl (E)-13-Octadecenalacetate acetate (E,Z)-8,10-Dodecadienal (E,Z)-8,10-Pentadecadien-1-ol(Z)-13-Octadecen-1-ol (Z,E)-8,10-Dodecadien-1-ol(E,Z)-8,10-Pentadecadienyl (Z)-13-Octadecenyl acetate acetate(Z,E)-8,10-Dodecadienyl (Z,E)-8,10-Pentadecadienyl (Z)-13-Octadecenalacetate acetate (Z,E)-8,10-Dodecadienal (Z,Z)-8,10-Pentadecadienyl(E)-14-Octadecenal acetate (Z,Z)-8,10-Dodecadien-1-ol(E,Z)-9,11-Pentadecadienal (E,Z)-2,13-Octadecadien-1-ol(Z,Z)-8,10-Dodecadienyl (Z,Z)-9,11-Pentadecadienal(E,Z)-2,13-Octadecadienyl acetate acetate (Z,E,E)-3,6,8-Dodecatrien-1-ol(Z)-3-Hexadecenyl acetate (E,Z)-2,13-Octadecadienal(Z,Z,E)-3,6,8-Dodecatrien-1-ol (E)-5-Hexadecen-1-ol(Z,E)-2,13-Octadecadienyl acetate (E)-2-Tridecenyl acetate(E)-5-Hexadecenyl acetate (Z,Z)-2,13-Octadecadien-1-ol (Z)-2-Tridecenylacetate (Z)-5-Hexadecen-1-ol (Z,Z)-2,13-Octadecadienyl acetate(E)-3-Tridecenyl acetate (Z)-5-Hexadecenyl acetate(E,E)-3,13-Octadecadienyl acetate (E)-4-Tridecenyl acetate(E)-6-Hexadecenyl acetate (E,Z)-3,13-Octadecadienyl acetate(Z)-4-Tridecenyl acetate (E)-7-Hexadecen-1-ol (E,Z)-3,13-Octadecadienal(Z)-4-Tridecenal (E)-7-Hexadecenyl acetate (Z,E)-3,13-Octadecadienylacetate (E)-6-Tridecenyl acetate (E)-7-Hexadecenal(Z,Z)-3,13-Octadecadienyl acetate (Z)-7-Tridecenyl acetate(Z)-7-Hexadecen-1-ol (Z,Z)-3,13-Octadecadienal (E)-8-Tridecenyl acetate(Z)-7-Hexadecenyl acetate (E,E)-5,9-Octadecadien-1-ol (Z)-8-Tridecenylacetate (Z)-7-Hexadecenal (E,E)-5,9-Octadecadienyl acetate(E)-9-Tridecenyl acetate (E)-8-Hexadecenyl acetate(E,E)-9,12-Octadecadien-1-ol (Z)-9-Tridecenyl acetate(E)-9-Hexadecen-1-ol (Z,Z)-9,12-Octadecadienyl acetate (Z)-10-Tridecenylacetate (E)-9-Hexadecenyl acetate (Z,Z)-9,12-Octadecadienal(E)-11-Tridecenyl acetate (E)-9-Hexadecenal (Z,Z)-11,13-Octadecadienal(Z)-11-Tridecenyl acetate (Z)-9-Hexadecen-1-ol(E,E)-11,14-Octadecadienal (E,Z)-4,7-Tridecadienyl (Z)-9-Hexadecenylacetate (Z,Z)-13,15-Octadecadienal acetate (Z,Z)-4,7-Tridecadien-1-ol(Z)-9-Hexadecenal (Z,Z,Z)-3,6,9-Octadecatrienyl acetate(Z,Z)-4,7-Tridecadienyl (E)-10-Hexadecen-1-ol (E,E,E)-9,12,15- acetateOctadecatrien-1-ol (E,Z)-5,9-Tridecadienyl (E)-10-Hexadecenal(Z,Z,Z)-9,12,15-Octadecatrienyl acetate acetate (Z,E)-5,9-Tridecadienyl(Z)-10-Hexadecenyl (Z,Z,Z)-9,12,15-Octadecatrienal acetate acetate

In certain embodiments, the invention provides a method for synthesizinga fatty olefin derivative as described above wherein the fatty olefinderivative is selected from (E)-7-dodecenal; (Z)-10-dodecenyl acetate;(Z)-10-hexadecenyl acetate; (Z)-10-pentadecenal; (Z)-10-pentadecenylacetate; (Z)-10-tetradecenyl acetate; (Z)-10-tridecenyl acetate;(Z)-7-decenyl acetate; (Z)-7-dodecenyl acetate; (Z)-7-hexadecenal;(Z)-7-hexadecenyl acetate; (Z)-7-tetradecenal; (Z)-7-tetradecenylacetate; (Z)-7-undecenyl acetate; (Z)-9-dodecenal; (Z)-9-dodecenylacetate; (Z)-9-hexadecenal; (Z)-9-hexadecenyl acetate;(Z)-9-pentadecenyl acetate; (Z)-9-tetradecenal; (Z)-9-tetradecenylacetate; (Z)-9-tetradecenyl formate; (Z)-9-tetradecenyl nitrate;(Z)-9-tridecenyl acetate; (Z)-9-undecenyl acetate;(E)-11-tetradecen-1-ol; (E)-11-tetradecenyl acetate; (E)-5-decen-1-ol;(E)-5-decenyl acetate; (E)-8-dodecen-1-ol; (E)-8-dodecenyl acetate;(Z)-11-hexadecen-1-ol; (Z)-11-hexadecenal; (Z)-11-hexadecenyl acetate;(Z)-11-tetraceden-1-ol; (Z)-11-tetracedenyl acetate;(Z)-13-octadecen-1-ol; (Z)-13-octadecenal; (Z)-3-hexanol;(Z)-3-nonen-1-ol; (Z)-5-decen-1-ol; (Z)-5-decenyl acetate;(Z)-7-dodecen-1-ol; (Z)-7-hexadecen-1-ol; (Z)-8-dodecen-1-ol;(Z)-8-dodecenyl acetate; (Z)-9-dodecen-1-ol; (Z)-9-hexadecen-1-ol; and(Z)-9-tetradecen-1-ol. In some such embodiments, the fatty olefinderivative is a pheromone.

In some embodiments, the fatty olefin derivative is selected from(E)-7-dodecenal; (Z)-10-dodecenyl acetate; (Z)-10-hexadecenyl acetate;(Z)-10-pentadecenal; (Z)-10-pentadecenyl acetate; (Z)-10-tetradecenylacetate; (Z)-10-tridecenyl acetate; (Z)-7-decenyl acetate;(Z)-7-dodecenyl acetate; (Z)-7-hexadecenal; (Z)-7-hexadecenyl acetate;(Z)-7-tetradecenal; (Z)-7-tetradecenyl acetate; (Z)-7-undecenyl acetate;(Z)-9-dodecenal; (Z)-9-dodecenyl acetate; (Z)-9-hexadecenal;(Z)-9-hexadecenyl acetate; (Z)-9-pentadecenyl acetate;(Z)-9-tetradecenal; (Z)-9-tetradecenyl acetate; (Z)-9-tetradecenylformate; (Z)-9-tetradecenyl nitrate; (Z)-9-tridecenyl acetate; and(Z)-9-undecenyl acetate. In some such embodiments, the fatty olefinderivative is a pheromone.

In some embodiments, the fatty olefin derivative is selected from(E)-7-dodecenal; (Z)-10-dodecenyl acetate; (Z)-10-hexadecenyl acetate;(Z)-10-pentadecenal; (Z)-10-pentadecenyl acetate; (Z)-10-tetradecenylacetate; (Z)-10-Tridecenyl acetate; (Z)-7-decenyl acetate;(Z)-7-hexadecenyl acetate; (Z)-7-tetradecenal; (Z)-7-tetradecenylacetate; (Z)-7-undecenyl acetate; (Z)-9-dodecenal; (Z)-9-pentadecenylacetate; (Z)-9-tetradecenal; (Z)-9-tetradecenyl formate;(Z)-9-tetradecenyl nitrate; (Z)-9-tridecenyl acetate; and(Z)-9-undecenyl acetate. In some such embodiments, the fatty olefinderivative is a pheromone.

As described above, the methods of the invention can also be used forthe synthesis of polyene derivatives, including polyene pheromones. See,for example, Scheme 6.

Polyene derivatives include dienes, trienes, and tetraenes. The doublebonds in the polyenes can be Z double bonds or E double bonds. Dienesthat can be prepared using the methods of the invention include, but arenot limited to, (6Z,9Z)-heptadeca-6,9-diene; (6Z,9Z)-octadeca-6,9-diene;(6Z,9Z)-nonadeca-6,9-diene; (6Z,9Z)-eicosa-6,9-diene;(6Z,9Z)-henicosa-6,9-diene; (6Z,9Z)-docosa-6,9-diene; and(6Z,9Z)-tricosa-6,9-diene. The dienes can be used as pheromones.

Trienes that can be prepared using the methods of the invention include,but are not limited to, (3Z,6Z,9Z)-heptadeca-3,6,9-triene;(3Z,6Z,9Z)-octadeca-3,6,9-triene; (3Z,6Z,9Z)-nonadeca-3,6,9-triene;(3Z,6Z,9Z)-eicosa-3,6,9-triene; (3Z,6Z,9Z)-henicosa-3,6,9-triene;(3Z,6Z,9Z)-docosa-3,6,9-triene; (3Z,6Z,9Z)-tricosa-3,6,9-triene;(4E,6Z,9Z)-heptadeca-4,6,9-triene; (4E,6Z,9Z)-octadeca-4,6,9-triene;(4E,6Z,9Z)-nonadeca-4,6,9-triene; (4E,6Z,9Z)-eicosa-4,6,9-triene;(4E,6Z,9Z)-henicosa-4,6,9-triene; (4E,6Z,9Z)-docosa-4,6,9-triene; and(4E,6Z,9Z)-tricosa-4,6,9-triene. The trienes can be used as pheromones.

Tetraenes that can be prepared using the methods of the inventioninclude, but are not limited to, (3Z,6Z,9Z)-heptadeca-1,3,6,9-tetraene;(3Z,6Z,9Z)-octadeca-1,3,6,9-tetraene;(3Z,6Z,9Z)-nonadeca-1,3,6,9-tetraene;(3Z,6Z,9Z)-eicosa-1,3,6,9-tetraene;(3Z,6Z,9Z)-henicosa-1,3,6,9-tetraene;(3Z,6Z,9Z)-docosa-1,3,6,9-tetraene; (3Z,6Z,9Z)-tricosa-1,3,6,9-tetraene;(3Z,6Z,9Z,11E/Z)-heptadeca-3,6,9,11-tetraene;(3Z,6Z,9Z,11E/Z)-octadeca-3,6,9,11-tetraene;(3Z,6Z,9Z,11E/Z)-nonadeca-3,6,9,11-tetraene; (3Z,6Z,9Z,11E/Z)-eicosa-3,6,9,11-tetraene;(3Z,6Z,9Z,11E/Z)-henicosa-3,6,9,11-tetraene;(3Z,6Z,9Z,11E/Z)-docosa-3,6,9,11-tetraene; and(3Z,6Z,9Z,11E/Z)-tricosa-3,6,9,11-tetraene. The tetraenes can be used aspheromones.

Polyene derivatives include oxidized polyenes such as ketones andepoxides. Examples of ketone polyene derivatives include, but are notlimited to: (6Z,9Z)-heptadeca-6,9-dien-3-one;(6Z,9Z)-octadeca-6,9-dien-3-one; (6Z,9Z)-nonadeca-6,9-dien-3-one;(6Z,9Z)-eicosa-6,9-dien-3-one; (6Z,9Z)-henicosa-6,9-dien-3-one;(6Z,9Z)-docosa-6,9-dien-3-one; and (6E,9E)-tricosa-6,9-dien-3-one.Examples of polyene epoxide derivatives include, but are not limited to3Z,6Z-9R,10S-epoxy-heneicosadiene, 3Z,6Z-9R,10S-epoxy-docosadiene, andthe like. The ketone polyene derivatives and the polyene epoxidederivatives can be used as pheromones. The structure, taxonomicdistribution, mechanisms of action, and biosynthetic pathways of polyenepheromones (including polyene epoxides) are described by Millar (Annu.Rev. Entomol. 2000. 45:575-604).

Pheromone Compositions and Uses Thereof

Pheromones prepared according to the methods of the invention can beformulated for use as insect control compositions. The pheromonecompositions can include a carrier, and/or be contained in a dispenser.The carrier can be, but is not limited to, an inert liquid or solid.

Examples of solid carriers include but are not limited to fillers suchas kaolin, bentonite, dolomite, calcium carbonate, talc, powderedmagnesia, Fuller's earth, wax, gypsum, diatomaceous earth, rubber,plastic, silica and China clay. Examples of liquid carriers include, butare not limited to, water; alcohols, such as ethanol, butanol or glycol,as well as their ethers or esters, such as methylglycol acetate;ketones, such as acetone, cyclohexanone, methylethyl ketone,methylisobutylketone, or isophorone; alkanes such as hexane, pentane, orheptanes; aromatic hydrocarbons, such as xylenes or alkyl naphthalenes;mineral or vegetable oils; aliphatic chlorinated hydrocarbons, such astrichloroethane or methylene chloride; aromatic chlorinatedhydrocarbons, such as chlorobenzenes; water-soluble or strongly polarsolvents such as dimethylformamide, dimethyl sulfoxide, orN-methylpyrrolidone; liquefied gases; and mixtures thereof. Baits orfeeding stimulants can also be added to the carrier.

Pheromone compositions can be formulated so as to provide slow releaseinto the atmosphere, and/or so as to be protected from degradationfollowing release. For example, the pheromone compositions can beincluded in carriers such as microcapsules, biodegradable flakes andparaffin wax-based matrices.

Pheromone compositions can contain other pheromones or attractantsprovided that the other compounds do not substantially interfere withthe activity of the composition. The pheromone compositions can alsoinclude insecticides. Examples of suitable insecticides include, but arenot limited to, buprofezin, pyriproxyfen, flonicamid, acetamiprid,dinotefuran, clothianidin, acephate, malathion, quinolphos,chloropyriphos, profenophos, bendiocarb, bifenthrin, chlorpyrifos,cyfluthrin, diazinon, pyrethrum, fenpropathrin, kinoprene, insecticidalsoap or oil, and mixtures thereof.

Pheromone compositions can be used in conjunction with a dispenser forrelease of the composition in a particular environment. Any suitabledispenser known in the art can be used. Examples of such dispensersinclude but are not limited to bubble caps comprising a reservoir with apermeable barrier through which pheromones are slowly released, pads,beads, tubes rods, spirals or balls composed of rubber, plastic,leather, cotton, cotton wool, wood or wood products that are impregnatedwith the pheromone composition. For example, polyvinyl chloridelaminates, pellets, granules, ropes or spirals from which the pheromonecomposition evaporates, or rubber septa. One of skill in the art will beable to select suitable carriers and/or dispensers for the desired modeof application, storage, transport or handling.

A variety of pheromones, including those set forth in Table 1 can beprepared according to the methods of the invention and formulated asdescribed above. For example, the methods of the invention can be usedto prepare peach twig borer (PTB) sex pheromone, which is a mixture of(E)-dec-5-en-1-ol (17%) and (E)-dec-5-en-1-yl acetate (83%). The PTB sexpheromone can be used in conjunction with a sustained pheromone releasedevice having a polymer container containing a mixture of the PTB sexpheromone and a fatty acid ester (such as a sebacate, laurate,palmitate, stearate or arachidate ester) or a fatty alcohol (such asundecanol, dodecanol, tridecanol, tridecenol, tetradecanol,tetradecenol, tetradecadienol, pentadecanol, pentadecenol, hexadecanol,hexadecenol, hexadecadienol, octadecenol and octadecadienol). Thepolymer container can be a tube, an ampule, or a bag made of apolyolefin or an olefin component-containing copolymer. Sex pheromonesof other pest insects such the cotton bollworm (Helicoverpa armigera),fall army worm (Spodoptera frugiperda), oriental fruit moth (Grapholitamolesta) and leaf roller (Tortricidae) can be used in this type ofsustained pheromone release device. The sex pheromones typically includeone or more aliphatic acetate compounds having from 10 to 16 carbonatoms (e.g., decyl acetate, decenyl acetate, decadienyl acetate, undecylacetate, undecenyl acetate, dodecyl acetate, dodecenyl acetate,dodecadienyl acetate, tridecyl acetate, tridecenyl acetate,tridecadienyl acetate, tetradecyl acetate, tetradecenyl acetate,tetradecadienyl acetate, and the like) and/or one or more aliphaticaldehyde compounds having from 10 to 16 carbon atoms (e.g.,7-hexadecenal, 11-hexadecenal, 13-octadecenal, and the like).

Pheromones prepared according to the methods of the invention, as wellas compositions containing the pheromones, can be used to control thebehavior and/or growth of insects in various environments. Thepheromones can be used, for example, to attract or repel male or femaleinsects to or from a particular target area. The pheromones can be usedto attract insects away from vulnerable crop areas. The pheromones canalso be used example to attract insects as part of a strategy for insectmonitoring, mass trapping, lure/attract-and-kill or mating disruption.

Mass trapping involves placing a high density of traps in a crop to beprotected so that a high proportion of the insects are removed beforethe crop is damaged. Lure/attract-and-kill techniques are similar exceptonce the insect is attracted to a lure, it is subjected to a killingagent. Where the killing agent is an insecticide, a dispenser can alsocontain a bait or feeding stimulant that will entice the insects toingest an effective amount of the insecticide.

It will be appreciated by a person skilled in the art that a variety ofdifferent traps are possible. Suitable examples of such traps includewater traps, sticky traps, and one-way traps. Sticky traps come in manyvarieties. One example of a sticky trap is of cardboard construction,triangular or wedge-shaped in cross-section, where the interior surfacesare coated with a non-drying sticky substance. The insects contact thesticky surface and are caught. Water traps include pans of water anddetergent that are used to trap insects. The detergent destroys thesurface tension of the water, causing insects that are attracted to thepan, to drown in the water. One-way traps allow an insect to enter thetrap but prevent it from exiting. The traps of the invention can becolored brightly, to provide additional attraction for the insects.

The trap is positioned in an area infested (or potentially infested)with insects. Generally, the trap is placed on or close to a tree orlarge plant and the pheromone attracts the insects to the trap. Theinsects can then be caught, immobilized and/or killed within the trap,for example, by the killing agent present in the trap.

Pheromones prepared according to the methods of the invention can alsobe used to disrupt mating. Strategies of mating disruption includeconfusion, trail-masking and false-trail following. Constant exposure ofinsects to a high concentration of a pheromone can prevent male insectsfrom responding to normal levels of the pheromone released by femaleinsects. Trail-masking uses a pheromone to destroy the trail ofpheromones released by females. False-trail following is carried out bylaying numerous spots of a pheromone in high concentration to presentthe male with many false trails to follow. When released in sufficientlyhigh quantities, the male insects are unable to find the natural sourceof the sex pheromones (the female insects) so that mating cannot occur.

Insect populations can be surveyed or monitored by counting the numberof insects in a target area (e.g., the number of insects caught in atrap). Inspection by a horticulturist can provide information about thelife stage of a population. Knowing where insects are, how many of themthere are, and their life stage enables informed decisions to be made asto where and when insecticides or other treatments are warranted. Forexample, a discovery of a high insect population can necessitate the useof methods for removal of the insect. Early warning of an infestation ina new habitat can allow action to be taken before the population becomesunmanageable. Conversely, a discovery of a low insect population canlead to a decision that it is sufficient to continue monitoring thepopulation. Insect populations can be monitored regularly so that theinsects are only controlled when they reach a certain threshold. Thisprovides cost-effective control of the insects and reduces theenvironmental impact of the use of insecticides.

As will be apparent to one of skill in the art, the amount of apheromone or pheromone composition used for a particular application canvary depending on several factors such as the type and level ofinfestation; the type of composition used; the concentration of theactive components; how the composition is provided, for example, thetype of dispenser used; the type of location to be treated; the lengthof time the method is to be used for; and environmental factors such astemperature, wind speed and direction, rainfall and humidity. Those ofskill in the art will be able to determine an effective amount of apheromone or pheromone composition for use in a given application.

IV. EXAMPLES Example 1. Cross-Metathesis of Dec-9-en-1-yl Acetate withHex-1-ene

Prior to introduction of the metathesis catalyst, dec-9-en-1-yl acetate(CAS #50816-18-7) and hex-1-ene (CAS #592-41-6) are treated with eitheraluminum oxide (Al₂O₃) or a trialkylaluminum as described in U.S. Pat.No. 9,388,097 to reduce moisture, peroxides, and other potentialcatalyst poisons to a level suitable for conducting the metathesisreaction. In a nitrogen-filled glovebox, a 20 mL scintillation vial ischarged with a magnetic stir bar, 1.00 g of pretreated dece-9-en-1-ylacetate and 1.27 g of pretreated hex-1-ene. The vial is closed with aperforated septum and placed in an aluminum heating block regulated at40° C. atop a hotplate/magnetic stirrer where the stirring rate is fixedat 500 rpm. A solution of1-({3,3′-dibromo-2′-[(tert-butyldimethylsilyl)oxy]-5H,5′H,6H,6′H,7H,7′H,8H,8′H-[1,1′-binaphthalene]-2-yl}oxy)-1-(2,5-dimethylpyrrol-1-yl)-1-(2-methyl-2-phenylpropylidene)-N-phenyltungstenimine(CAS #1628041-76-8) catalyst in dry and degassed toluene is prepared byweighing 10 mg of the catalyst into a 1 mL volumetric flask and dilutingto the calibration mark with solvent. Using a gas tight microlitersyringe, 57 μL of the catalyst solution (0.57 mg, 0.025 wt %, 0.0025 mol%) is withdrawn from the volumetric flask and added to the reactionmixture. After four hours, the vial is removed from the glovebox and thereaction mixture is analyzed by GC-MS. The GC-MS data indicates that(Z)-tetradec-9-en-1-yl acetate is formed in high yield.

Example 2. Cross-Metathesis of Methyl Dec-9-enoate with Oct-1-ene

Prior to introduction of the metathesis catalyst, methyl dec-9-enoate(CAS #25601-41-6) and oct-1-ene (CAS #111-66-0) are treated to reducemoisture, peroxides and other potential catalyst poisons to a levelsuitable for conducting the metathesis reaction as described in U.S.Pat. No. 9,388,097. In a nitrogen-filled glovebox, a 20 mL scintillationvial is charged with a magnetic stir bar, 1.00 g of pretreated methyldec-9-enoate and 1.83 g of pretreated oct-1-ene. The vial is closed witha perforated septum and placed in an aluminum heating block regulated at40° C. atop a hotplate/magnetic stirrer where the stirring rate is fixedat 500 rpm. A solution of1-({3,3′-dibromo-2′-[(tert-butyldimethylsilyl)oxy]-5H,5′H,6H,6′H,7H,7′H,8H,8′H-[1,1′-binaphthalene]-2-yl}oxy)-1-(2,5-dimethylpyrrol-1-yl)-1-(2-methyl-2-phenylpropylidene)-N-phenyltungstenimine(CAS #1628041-76-8)catalystin dry and degassed toluene is prepared byweighing 10 mg of the catalyst into a 1 mL volumetric flask and dilutingto the calibration mark with solvent. Using a gas tight microlitersyringe, 71 μL of the catalyst solution (0.71 mg cat., 0.025 wt %,0.0029 mol %) is withdrawn from the volumetric flask and added reactionmixture. After four hours the vial is removed from the glovebox and thereaction mixture is analyzed by GC-MS. The GC-MS data indicates thatmethyl (Z)-hexadec-9-enoate is formed in high yield.

Example 3. Reduction of Methyl Hexadec-9-enoate with SodiumBis(2-methoxyethoxy) Aluminumhydride

In an oven-dried, nitrogen-flushed flask sealed with a rubber septum andcontaining a magnetic stir bar is added 0.47 g N-methylpiperazine (CAS#109-01-3) and 10 mL of dry, degassed toluene. The flask is submerged inan ice bath and, with magnetic stirring, 1.48 g of a 70% solution ofsodium bis(2-methoxyethoxy)aluminumhydride (CAS #22722-98-1) in tolueneis added dropwise. In a separate oven dried, nitrogen-flushed flasksealed with a rubber septum is added 1.00 g of methyl hexadec-9-enoate,prepared through the process detailed in Example 2, and 20 mL of dry,degassed toluene. The flask is then submerged in an ice bath and stirrervia an external magnetic stirrer. After stirring for one hour, theN-methylpiperazine/sodium bis(2-methoxyethoxy)aluminumhydride mixture isadded dropwise via a cannula to the toluene solution of ester. Theresulting mixture is stirred at ice-bath temperature for one hour andthen brought to ambient temperature and stirred for an additional hour.The reaction is quenched by addition of 20 mL of deionized water andthen extracted with 20 mL of EtOAc. The organic layer is washed with 20mL of deionized water, dried over sodium sulfated and then concentratedin vacuo. The product is analyzed by GC-MS, indicating that(Z)-hexadec-9-enal is formed in high yield.

Example 4. Preparation of Eicosa-3,6,9-triene, a Polyene Pheromone

Prior to introduction of metathesis catalysts, linseed oil (CAS#8001-26-1) and dodec-1-ene (CAS #112-41-4) are treated to reducemoisture, peroxides and other potential catalyst poisons to the desiredlevel. In a nitrogen-filled glovebox, a 20 mL scintillation vial ischarged with a magnetic stir bar, 1.00 g of pretreated linseed oil and0.481 g of pretreated dec-1-ene. The vial is closed with a perforatedseptum and placed in an aluminum heating block regulated at 40° C. atopa hotplate/magnetic stirrer where the stirring rate is fixed at 500 rpm.A solution of1-({3,3′-dibromo-2′-[(tert-butyldimethylsilyl)oxy]-5H,5′H,6H,6′H,7H,7′H, 8H,8′H-[1,1′-binaphthalene]-2-yl}oxy)-1-(2,5-dimethylpyrrol-1-yl)-1-(2-methyl-2-phenylpropylidene)-N-phenyltungstenimine(CAS #1628041-76-8) in dry and degassed toluene is prepared by weighing10 mg of the catalyst into a 1 mL volumetric flask and diluting to thecalibration mark with solvent. Using a gas tight microliter syringe, 37μL (0.37 mg cat., 0.025 wt %, 0.0071 mol %) of the catalyst solution iswithdrawn from the volumetric flask and added reaction mixture. Afterone hour the vial is removed from the glovebox. The reaction mixture istransesterified with methanol using sodium methoxide as a catalyst priorto analysis by GC-MS. The transesterified reaction mixture contains thedesired eicosa-3,6,9-triene product (CAS #134370-60-8), as well as smallamounts of 1,18-dimethyl octadec-9-enedioate (CAS #13481-97-5), methyleicos-9-enoate (CAS #10340-21-3), docos-11-ene (CAS #62978-77-2), andcyclohexa-1,4-diene (CAS #628-41-1).

Example 5. Metathesis Catalyst Screening for the Z-SelectiveCross-Metathesis of Methyl Dec-9-enoate and Hex-1-ene

In a nitrogen-filled glovebox, a 30 mL glass vial was charged a with amagnetic stir bar and 2.70 g of an equimolar mixture of methyldec-9-enoate and hex-1-ene previously treated with activated basicalumina to reduce levels of moisture, peroxide and protic impurities inthe method described in U.S. Ser. No. 14/209,686. To the olefin mixturewas added 0.0025 mol % of a molybdenum or tungsten metathesis catalystsas a toluene solution. The vial was then closed with a perforated capand the reaction mixtures were stirred by means of a magnetic hotplatestirrer for a total of four hours after the addition of catalyst.Aliquots of the reaction mixture were taken at one and four hours afterthe addition of catalyst and analyzed to determine 9-DAME conversion (%)and methyl (Z)-tetradec-9-enoate selectivity (%) (Table 8) by GC-MS/FIDafter using the equations below in conjuction with external calibrationcurves obtained for the analytes of interest. GC chromatograms wererecorded using a Shimadzu GC2010 Plus instrument equipped with anAgilent DB-23 capillary column with a length of 30 m, an inner diameterof 0.25 mm and a film thickness of 0.25 μm. Nitrogen was used as thecarrier gas and the total flow of gas through the column was 61.9mL/min. Injections were split at a 1:30 ratio with the carrier gas andthe injector of the instrument was maintained at a constant temperatureof 240° C. The oven temperature was held at 35° C. during the injectionand for the following five minutes, then raised to 100° C. at a rate of35° C./min, raised further to 130° C. at a rate of 7° C./min, raisedagain to 240° C. at a rate of 35° C./min and finally held at thisterminal temperature for 3.71 minutes for a total run length of approx.18 minutes.

${{{Methyl}\mspace{14mu}{Dec}} - 9 - {{enoate}\mspace{14mu}{Conversion}\mspace{14mu}(\%)}} = {1 - {\left( \frac{{{Final}\mspace{14mu}{mol}\mspace{14mu}{Methyl}\mspace{14mu}{Dec}} - 9 - {enoate}}{{{Initial}\mspace{14mu}{mol}\mspace{14mu}{Methyl}\mspace{14mu}{Dec}} - 9 - {enoate}} \right) \times 100}}$${{{Methyl}(Z)} - {Tetradec} - 9 - {{enoate}\mspace{14mu}{Selectivity}\mspace{11mu}(\%)}} = {\left( \frac{{{mol}\mspace{14mu}{Methyl}\mspace{11mu}(Z)} - {Tetradec} - 9 - {enoate}}{\begin{matrix}{{{mol}\mspace{14mu}{Methyl}\mspace{11mu}(Z)} - {Tetradec} - 9 - {enoate} +} \\{{{mol}\mspace{14mu}{{Methyl}(E)}} - {Tetradec} - 9 - {enoate}}\end{matrix}} \right) \times 100}$

TABLE 8 4 Hour Reaction Length 24 Hour Reaction Length Methyl Dec-9-Methyl (Z)-Tetradec- Methyl Dec-9- Methyl (Z)-Tetradec- enoateConversion 9-enoate Selectivity enoate Conversion 9-enoate SelectivityCatalyst (%) (%) (%) (%) 1 40 91 73 90 2 56 94 70 93 3 67 95 68 95 4 5116 52 16 5 21 95 28 94 6 47 94 54 94 7 <0.1 Not Determined <0.1 NotDetermined 8 <0.1 Not Determined <0.1 Not Determined 9 15 95 17 95 10 5293 60 93 Catalyst Structure Formula 1

C54H70Br2MoN2O2Si 2

C50H62Br2MoN2O2Si 3

C52H68Br2MoN2O2Si 4

C52H68Br2MoN2OSi 5

C50H59FMoN2O 6

C46H52Br2Cl2N2O3 SiW 7

C48H56NO2PW 8

C54H52NO2PW 9

C50H60MoN2O 10 C54H50N2OW Ph = phenyl, C6H5; Mes =2,4,6-trimethylphenyl, 2,4,6-Me3C6H2; TBS = tert-butyldimethylsilyl,SiMe2(t-Bu)

Example 6. Synthesis and Isolation of Methyl (Z)-Tetradec-9-enoate ViaCross-Metathesis of Methyl Dec-9-enoate and Hex-1-ene

Into a glass vessel equipped with an agitator, thermometer and refluxcondenser, were charged 500 g of methyl dec-9-enoate (2.71 mol) and 480g of hex-1-ene (5.70 mol). To the thoroughly homogenized feedstocks asolution of triethylaluminum in toluene (3.82 g, 0.0335 mol, 0.389 mol%) was added in one portion. After agitating at 500 rpm for an hour at23-25° C., the temperature of the feedstock was raised to 40-41° C.0.121 g (0.00128 mol %, 123 ppmwt) of tungsten,[(1R)-3,3′-dibromo-2′-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-5,5′,6,6′,7,7′,8,8′-octahydro[1,1′-binaphthalen]-2-olato-κO][2,6-dichlorobenzenaminato(2-)-κN](2,5-dimethyl-1H-pyrrol-1-yl)[(2-methoxyphenyl)methylene]-, (T-4)-(CAS#1817807-15-0) was added in four portions to control the rate ofethylene generation and the reaction was allowed to proceed for threehours. After that time GC-FID analysis showed the reaction proceed in57% Methyl Dec-9-enoate Conversion and 96% Methyl (Z)-tetradec-9-enoateSelectivity. To the cooled (25-30° C.) reaction mixture was added 10 mLof methanol (H₂O=0.035-0.038 w %). The mixture was stirred at ambienttemperature for 15-20 minutes. The aliquot was then removed from thereactor and filtered through a plug comprising a lower 0.5 cm layer ofdiatomaceous earth and an upper 1.0 cm layer of silica gel. The filtercake was washed with 7×100 mL MTBE. The volume of the colorless andclear filtrate was concentrated under reduced pressure in a 45° C. waterbath at a pressure of 40 mbar to obtain the crude product as a colorlessliquid. The crude material was vacuum distilled (0.2-1 mbar) using ashort path distillation apparatus and 166 g (25% overall yield) ofmethyl (Z)-tetradec-9-enoate was collected at a head temperature of95-97° C. and pressure of 0.4 mbar.

Example 7. Reduction of Methyl (Z)-tetradec-9-enoate to(Z)-tetradec-9-en-1-ol Using Sodium Bis(2-methoxyethoxy) Aluminumhydride

In an oven dried, nitrogen-flushed flask sealed with a rubber septum andcontaining a magnetic stir bar was added 240 g (0.831 mol ‘AlH₂’, 1.2eq.) of a 70% solution of sodium bis(2-methoxyethoxy)aluminumhydride(CAS #22722-98-1) in toluene. The flask is then submerged in an ice bathand stirred via an external magnetic stirrer and 166 g (0.691 mol) ofmethyl (Z)-tetradec-9-enoate, prepared through the process detailed inExample 6, was slowly added. The resulting mixture is stirred atice-bath temperature for one hour and then brought to ambienttemperature and stirred for an additional hour. The reaction mixture wasthen quenched with 10 mL deionized water and acidified with 15 w/w %aqueous sulfuric acid until the pH of the aqueous layer was 4. Theobtained slurry was filtered through diatomaceous earth and the filtercake was rinsed with 2×150 mL of toluene. The two phases of the motherliquor were separated. The aqueous layer was washed with additional 300mL of toluene. The combined organic phases were washed with 1500 mLdeionized water. All volatile components were removed by in vacuo andthe product dried via azeotropic distillation with additional toluene toyield 144 g (0.678 mol, 98% yield).

Example 8. Synthesis of (Z)-tetradec-9-en-1-yl Acetate throughEsterification of (Z)-tetradec-9-en-1-ol to with Acetic Anhydride

In an oven dried, nitrogen-flushed flask sealed with a rubber septum andcontaining a magnetic stir bar was added 144 g (0.678 mol) of(Z)-tetradec-9-en-1-ol, prepared through the method detailed in Example7, 75.9 g of acetic anhydride (0.743 mol) and 5.50 g of sodium acetate(0.067 mol, 0.1 eq.). The reaction mixture was then heated to 60° C. forone hour, cooled and then washed consecutively with water and a sodiumcarbonate solution, yielding 160 g (0.629 mol, 92% yield) of(Z)-tetradec-9-en-1-yl acetate as a colorless liquid.

Example 9. Acetylation of 7-octen-1-ol with Acetic Anhydride

7-octen-1-ol (46.49 g, 363 mmol), first purified via vacuum distillation(72° C./8 mbar), was charged into a three-necked, round-bottomed flaskequipped with a thermometer, a reflux condenser and a magnetic stirrerbar. The top of the condenser was connected to a Schlenk line and thewhole apparatus was flushed with nitrogen. Acetic anhydride (44.29 g,434 mmol) and anhydrous sodium acetate (3.25 g, 39.7 mmol) were added tothe flask. The mixture was stirred at 68° C. for 4 hours. GC showedcomplete conversion. 200 mL of DCM was added to the reaction mixture andmixed with water (100 mL). NaHCO₃ (25 g) was carefully and portion-wiseadded to adjust the pH of the aqueous phase to 6. The organic phase wasseparated and extracted with saturated solution of NaHCO₃ (pH˜8-9) thenwith 100 mL of water (pH˜7). The separated DCM fraction was dried overNa₂SO₄ (60 g) and Na₂CO₃ (6 g) for one night. Organic phase wascollected filtered, solid was washed with DCM and hexane. Volatiles wereremoved on rotary evaporator and the crude product further dried at 60°C./10 mbar for 4 hours. The material was then vacuum distilled a (79-80°C./10 mbar) to yield 51.53 g (83% yield) of a colorless liquid wasobtained.

Example 10. Cross-Metathesis of Oct-7-en-1-yl Acetate with Hex-1-ene

In a nitrogen-filled glovebox, a 20 mL scintillation vial was chargedwith a magnetic stir bar, 1.315 g of oct-7-en-1-yl acetate (CAS#5048-35-1) and finally 0.685 g of hex-1-ene (1.05 equivalents). Thevial was then closed with a perforated septum. The feedstock was treatedwith 69 μL of a 25 wt % solution of triethylaluminum in toluene (14.4 mgAlEt₃, 0.720 wt %, 0.803 mol %) and the mixture stirred via an externalmagnetic stirrer at room temperature for four hours. To the mixture wasthen added 0.002 mol % (0.35 mg, 0.0177 wt %) of tungsten[(1R)-3,3′-dibromo-2′-[[(1,1-dimethylethy)dimethylsilyl]oxy]-5,5′,6,6′,7,7′,8,8′-octahydro[1,1′-binaphthalen]-2-olato-κO][2,6-dichlorobenzenaminato(2-)-κN](2,5-dimethyl-1H-pyrrol-1-yl)[(2-methoxyphenyl)methylene]-, (T-4)-(CAS#1817807-15-0) as a solution in benzene. At the time after theadditional of catalyst specified in the table below, an aliquot of thereaction mixture was removed from the glovebox and analyzed byGC-MS/FID. The results of the GC-MS/FID analysis of these samples ispresented in the table below:

Time After Approximate Conversion of Approximate Catalyst Oct-7-en-1-ylAcetate to (Z)-Dodec-7-en-1-yl Addition (h) Dodec-7-en-1-yl Acetate (%)Acetate Content (%) 1 34 97 4 37 97 6 38 97 24 38 97

Example 11. Cross-Metathesis of Oct-7-en-1-yl Acetate with Hex-1-ene

Prior to conducting the procedure below, the oct-7-en-1-yl acetate wasfurther purified through a second vacuum distillation to removeadditional catalyst deactivating impurities. In a nitrogen-filledglovebox, a 20 mL scintillation vial was charged with a magnetic stirbar, 1.338 g of oct-7-en-1-yl acetate (CAS #5048-35-1) and finally 0.662g of hex-1-ene. The vial was then closed with a perforated septum. Thefeedstock was treated with 7.4 μL of a 25 wt % solution oftriethylaluminum in toluene (1.54 mg AlEt₃, 0.0769 wt %, 0.0857 mol %)and the mixture stirred via an external magnetic stirrer at roomtemperature for four hours. To the mixture was then added 0.002 mol %(0.35 mg, 0.0177 wt %) of tungsten[(1R)-3,3′-dibromo-2′-[[(1,1-dimethylethy)dimethylsilyl]oxy]-5,5′,6,6′,7,7′,8,8′-octahydro[1,1′-binaphthalen]-2-olato-κO][2,6-dichlorobenzenaminato(2-)-κN](2,5-dimethyl-1H-pyrrol-1-yl)[(2-methoxyphenyl)methylene]-,(T-4)-(CAS #1817807-15-0) was added as a solution in benzene. At thetime after the additional of catalyst specified in the table below, analiquot of the reaction mixture was removed from the glovebox andanalyzed by GC-MS/FID. The results of the GC-MS/FID analysis of thesesamples is presented in the table below:

Time After Approximate Conversion of Approximate Catalyst Oct-7-en-1-ylAcetate to (Z)-Dodec-7-en-1-yl Addition (h) Dodec-7-en-1-yl Acetate (%)Acetate Content (%) 1 47 97 2 62 97 4 72 96 8 80 96 72 83 96

Example 12. Reduction of Methyl Dec-9-enoate to Dec-9-en-1-ol UsingSodium bis(2-methoxyethoxy) Aluminumhydride

In an oven dried, nitrogen-flushed flask sealed with a rubber septum andcontaining a magnetic stir bar was added 96.0 mL (353 mmol ‘AlH₂’, 1.3eq.) of a 70% solution of sodium bis(2-methoxyethoxy)aluminumhydride(CAS #22722-98-1) in toluene. The flask is then submerged in an ice bathand stirred via an external magnetic stirrer and 50 g (271 mmol) ofmethyl dec-9-enoate was slowly added so as to maintain the temperatureof the reaction mixture below 15° C. The resulting mixture is stirred atice-bath temperature for one hour and then brought to ambienttemperature and stirred for an additional hour. The reaction mixture wasthen quenched with 10 mL deionized water and acidified with 15 w/w %aqueous sulfuric acid until the pH of the aqueous layer was 4. Theobtained slurry was filtered through diatomaceous earth and the filtercake was rinsed with 2×50 mL of toluene. The two phases of the motherliquor were separated. The aqueous layer was washed with additional 100mL of toluene. The combined organic phases were washed with 50 mLdeionized water. All volatile components were removed by in vacuo andthe product dried via azeotropic distillation with additional toluene toyield 42.9 g of a colorless oil. This oil was later determined tocontain 96.0 wt % of dec-9-en-ol (97.1% yield) by GC-MS/FID analysis.

Example 13. Acetylation of 9-decen-1-ol

9-Decen-1-ol (50.0 g, 320 mmol), prepared through the method of Example13, was charged into a three-necked, round-bottomed flask equipped witha thermometer, a reflux condenser and a magnetic stirrer bar. The top ofthe condenser was connected to a Schlenk line and the whole apparatuswas flushed with nitrogen. Acetic anhydride (33 mL, 352 mmol, 1.1 eq.)and anhydrous sodium acetate 2.6 g, 32 mmol) were added to the flask.The mixture was stirred at 68° C. for 4 hours. GC showed completeconversion. 100 mL of DCM was added to the reaction mixture and mixedwith water (100 mL). NaHCO₃(25 g) was carefully and portion-wise addedto adjust the pH of the aqueous phase to 6. The organic phase wasseparated and extracted with saturated solution of NaHCO₃ (pH˜8-9) thenwith 100 mL of water (pH˜7). The separated DCM fraction was dried overNa₂SO₄ (60 g) and Na₂CO₃ (6 g) for one night. Organic phase wascollected filtered, solid was washed with DCM and hexane. All volatilecomponents were removed on rotary evaporator to yield 63.6 g of acolorless oil. This oil was later determined to contain 95.8 wt % ofdec-9-en-ol (95.6% yield).

Example 14. Cross-Metathesis of Dec-9-en-1-yl Acetate with Hex-1-ene

In a nitrogen-filled glovebox, a 20 mL scintillation vial was chargedwith a magnetic stir bar, 1.404 g of dec-9-en-1-yl acetate preparedthrough the method of Example 14 and finally 0.596 g of hex-1-ene. Thevial was then closed with a perforated septum. The feedstock was treatedwith 42.7 μL of a 25 wt % solution of triethylaluminum in toluene (0.9mg AlEt₃, 0.444 wt %, 0.541 mol %) and the mixture stirred via anexternal magnetic stirrer at room temperature for four hours. To themixture was then added 0.002 mol % (0.32 mg, 0.0159 wt %) of tungsten[(1R)-3,3′-dibromo-2′-[[(1,1-dimethylethy)dimethylsilyl]oxy]-5,5′,6,6′,7,7′,8,8′-octahydro[1,1′-binaphthalen]-2-olato-κO][2,6-dichlorobenzenaminato(2-)-κN](2,5-dimethyl-1H-pyrrol-1-yl)[(2-methoxyphenyl)methylene]-, (T-4)-(CAS#1817807-15-0) as a solution in benzene. At the time after theadditional of catalyst specified in the table below, an aliquot of thereaction mixture was removed from the glovebox and analyzed byGC-MS/FID. The GC-MS/FID data indicated that 23.9% of the startingdec-9-en-1-yl acetate was converted to tetradec-9-en-1-yl acetate and inan E/Z ratio of 3/97.

Example 15. Effect of Metathesis Catalyst Loading on the Z-SelectiveCross-Metathesis of Methyl Dec-9-enoate and Hex-1-ene

In a nitrogen-filled glovebox, five 30 mL scintillation vial werecharged with a magnetic stir bar, 2.70 g of an equimolar mixture ofmethyl dec-9-enoate and hex-1-ene. The vial was then closed with aperforated septum. The feedstock was treated with 11 μL of a 25 wt %solution of triethylaluminum in toluene (2.3 mg AlEt₃, 0.085 wt %, 0.1mol %) and the mixture stirred via an external magnetic stirrer at roomtemperature for 18 hours. To the mixture was added the amount oftungsten [(1R)-3,3′-dibromo-2′-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-5,5′,6,6′,7,7′,8,8′-octahydro[1,1′-binaphthalen]-2-olato-κO][2,6-dichlorobenzenaminato(2-)-κN](2,5-dimethyl-1H-pyrrol-1-yl)[(2-methoxyphenyl)methylene]-, (T-4)-(CAS #1817807-15-0) listed in thetable below as a solution in benzene. At the time after the addition ofcatalyst specified in the table below, an aliquot of the reactionmixture was removed from the glovebox and analyzed by GC-MS/FID todetermine ‘9-DAME Conversion (%)’ and ‘Methyl (Z)-tetradec-9-enoateSelectivity (%)’ as described in Example 5.

Catalyst Methyl Methyl Loading Time Dec-9-enoate (Z)-Tetradec-9-enoate(mol %) (h) Conversion (%) Selectivity (%) 0.0005 1 31 99 4 58 98 8 5997 0.001 1 38 98 4 76 97 8 76 96 0.0015 1 54 98 4 72 95 8 75 94 0.002 166 98 4 82 93 8 84 90 0.0025 1 72 97 4 84 91 8 88 88

Example 16. Cross-Metathesis of Oct-7-en-1-yl Acetate with Oct-1-ene

Using the method of Example 1, an equimolar amount of oct-7-en-1-ylacetate and oct-1-ene are charged into a 20 mL glass scintillation vialequipped with a magnetic stir bar inside of a nitrogen-filled glovebox.The mixture is then stirred by means of an external hotplate stirrer andis then treated with an alkyl aluminum reagent to reduce levels ofmoisture, peroxide and protic impurities as described in U.S. Pat. No.9,388,097. After sufficient time to ensure the removal of catalystdeactivating impurities to the desired level, the temperature of thesubstrate mixture is raised to the desired level and a sufficientquantity of a Z-selective group 6 metathesis catalyst to generate thedesired level of ‘Methyl Dec-9-enoate Conversion (%)’, as defined inExample 5, is added to the pretreated substrates. After the requiredamount of time, the vial is removed from the glovebox and the reactionmixture is analyzed by GC-MS. The GC-MS data indicates that(Z)-tetradec-7-en-1-yl acetate is formed in high yield.

Example 17. Cross-Metathesis of Oct-7-en-1-yl Acetate with But-1-ene

Using the method of Example 1, an equimolar amount of oct-7-en-1-ylacetate and but-1-ene are charged into a glass pressure vessel equippedwith a magnetic stir bar. The mixture is then stirred by means of anexternal hotplate stirrer and treated with an alkyl aluminum reagent toreduce levels of moisture, peroxide and protic impurities as describedin U.S. Pat. No. 9,388,097. After sufficient time to ensure the removalof catalyst deactivating impurities to the desired level, thetemperature of the substrate mixture is raised to the appropriatetemperature and a sufficient quantity of a Z-selective group 6metathesis catalyst to generate the desired level of ‘MethylDec-9-enoate Conversion (%)’, as defined in Example 5, is added to thepretreated substrates. After the required amount of time, the vial isremoved from the glovebox and the reaction mixture is analyzed by GC-MS.The GC-MS data indicates that (Z)-dec-7-en-1-yl acetate is formed inhigh yield.

Example 18. Cross-Metathesis of Dec-9-en-1-yl Acetate with Oct-1-ene

Using the method of Example 1, an equimolar amount of dec-9-en-1-ylacetate and oct-1-ene are charged into a 20 mL glass scintillation vialequipped with a magnetic stir bar inside of a nitrogen-filled glovebox.The mixture is then stirred by means of an external hotplate stirrer andis then treated with an alkyl aluminum reagent to reduce levels ofmoisture, peroxide and protic impurities as described in U.S. Pat. No.9,388,097. After sufficient time to ensure the removal of catalystdeactivating impurities to the desired level, the temperature of thesubstrate mixture is raised to the desired level and a sufficientquantity of a Z-selective group 6 metathesis catalyst to generate thedesired level of ‘Methyl Dec-9-enoate Conversion (%)’, as defined inExample 5, is added to the pretreated substrates. After the requiredamount of time, the vial is removed from the glovebox and the reactionmixture is analyzed by GC-MS. The GC-MS data indicates that(Z)-hexadec-9-en-1-yl acetate is formed in high yield.

Example 19. Cross-Metathesis of Dec-9-en-1-yl Acetate with But-1-ene

Using the method of Example 1, an equimolar amount of dec-9-en-1-ylacetate and but-1-ene are charged into a glass pressure vessel equippedwith a magnetic stir bar. The mixture is then stirred by means of anexternal hotplate stirrer and treated with an alkyl aluminum reagent toreduce levels of moisture, peroxide and protic impurities as describedin U.S. Pat. No. 9,388,097. After sufficient time to ensure the removalof catalyst deactivating impurities to the desired level, thetemperature of the substrate mixture is raised to the desired level anda sufficient quantity of a Z-selective group 6 metathesis catalyst togenerate the desired level of ‘Methyl Dec-9-enoate Conversion (%)’, asdefined in Example 5, is added to the pretreated substrates. After therequired amount of time, the vial is removed from the glovebox and thereaction mixture is analyzed by GC-MS. The GC-MS data indicates that(Z)-dodec-9-en-1-yl acetate is formed in high yield.

V. Exemplary Embodiments

Exemplary embodiments provided in accordance with the presentlydisclosed subject matter include, but are not limited to, the claims andthe following embodiments:

-   -   1. A method for synthesizing a fatty olefin derivative, the        method comprising:    -   a) contacting an olefin according to Formula I

-   -   with a metathesis reaction partner according to Formula IIb

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form a metathesis product according to Formula        IIIb:

and

-   -   b) converting the metathesis product to the fatty olefin        derivative;    -   wherein:    -   each R¹ is independently selected from the group consisting of        H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl;    -   R^(2b) is C₁₋₈ alkyl;    -   subscript y is an integer ranging from 0 to 17; and    -   subscript z is an integer ranging from 0 to 17.    -   2. The method of embodiment 1, wherein converting the metathesis        product to the fatty olefin derivative comprises reducing the        metathesis product to form an alkenol according to Formula Vb:

-   -   3. The method of embodiment 2, wherein the alkenol is the fatty        olefin derivative.    -   4. The method of embodiment 2, wherein converting the metathesis        product to the fatty olefin derivative further comprises        acylating the alkenol, thereby forming a fatty olefin derivative        according to Formula VIb:

-   -   wherein R^(2c) is C₁₋₆ acyl.    -   5. The method of any one of embodiments 1-3, wherein R¹ is H,        R^(2b) is methyl, subscript y is 7, and subscript z is 3.    -   6. The method of embodiment 4, wherein R¹ is H, R^(2b) is        methyl, subscript y is 7, subscript z is 3, and R^(2c) is        acetyl.    -   7. The method of embodiment 2, wherein converting the metathesis        product to the fatty olefin derivative further comprises        oxidizing the alkenol, thereby forming a fatty olefin derivative        according to Formula VIIb:

-   -   8. The method of embodiment 1, wherein converting the metathesis        product to the fatty olefin derivative further comprises        reducing the metathesis product, thereby forming a fatty olefin        derivative according to Formula VIIb:

-   -   9. The method of embodiment 7 or embodiment 8, wherein R¹ is H,        R^(2b) is methyl, subscript y is 7, and subscript z is 3.    -   10. The method of any one of embodiments 1-9, wherein the olefin        has a structure according to Formula 1a:

-   -   11. The method of embodiment 10, wherein subscript z is 3.    -   12. The method of any one of embodiments 1-11, wherein the        metathesis product comprises a Z olefin.    -   13. The method of embodiment 12, wherein at least about 80% of        the olefin is a Z olefin.    -   14. The method of embodiment 12, wherein at least about 90% of        the olefin is a Z olefin.    -   15. The method of any one of embodiments 12-14, wherein the        metathesis catalyst is a Z-selective molybdenum catalyst or a        Z-selective tungsten catalyst.    -   16. The method of embodiment 15, wherein the metathesis catalyst        has a structure according to Formula 2:

-   -   wherein:    -   M is Mo or W;    -   R^(3a) is selected from the group consisting of aryl,        heteroaryl, alkyl, heteroalkyl, cycloalkyl, and        heterocycloalkyl, each of which is optionally substituted;    -   R^(4a) and R^(5a) are independently selected from the group        consisting of hydrogen, optionally substituted alkyl, optionally        substituted alkenyl, optionally substituted heteroalkyl,        optionally substituted heteroalkenyl, optionally substituted        aryl, and optionally substituted heteroaryl;    -   R^(7a) is selected from the group consisting of alkyl, alkoxy,        heteroalkyl, aryl, aryloxy, heteroaryl, silylalkyl, and        silyloxy, each of which is optionally substituted; and    -   R^(6a) is R^(8a)—X—, wherein    -   X is O or S and R^(8a) is optionally substituted aryl; or    -   X is O and R^(8a) is SiR^(9a)R^(10a)R^(11a) or        CR^(12a)R^(13a)R^(14a), wherein R^(9a), R^(10a), R^(11a),        R^(12a), R^(13a), and R^(14a) are independently selected from        the group consisting of optionally substituted alkyl and        optionally substituted phenyl; or    -   R^(6a) and R^(7a) are linked together and are bonded to M via        oxygen.    -   17. The method of embodiment 16, wherein:    -   R^(7a) is selected from the group consisting of alkyl, alkoxy,        heteroalkyl, aryl, aryloxy, and heteroaryl, each of which is        optionally substituted; and    -   X is O or S and R^(8a) is optionally substituted aryl; or    -   X is O and R^(8a) is CR^(12a)R^(13a)R^(14a).    -   18. The method of embodiment 16, wherein    -   R^(3a) is selected from the group consisting of        2,6-dimethylphenyl; 2,6-diisopropylphenyl; 2,6-dichlorophenyl;        and adamant-1-yl;    -   R^(4a) is selected from the group consisting of —C(CH₃)₂C₆H₅ and        —C(CH₃)₃;    -   R^(5a) is H;    -   R^(7a) is selected from the group consisting of pyrrol-1-yl;        2,5-dimethyl-pyrrol-1-yl; triphenylsilyloxy;        triisopropylsilyloxy;        2-phenyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy;        2-methyl-1,1,1,3,3,3-hexafluoro-prop-2-yloxy;        9-phenyl-fluorene-9-yloxy; 2,6-diphenylphenoxy; and t-butyloxy;        and    -   R^(6a) is R^(8a)—X—, wherein    -   X═O and    -   R^(8a) is phenyl which bears two substituents in the ortho        positions with respect to O, or which bears at least three        substituents, from which two substituents are in the ortho        positions with respect to O and one substituent is in the para        position with respect to O; or    -   R^(8a) is selected from the group consisting of optionally        substituted 8-(naphthalene-1-yl)-naphthalene-1-yl; optionally        substituted 8-phenlynaphthalene-1-yl; optionally substituted        quinoline-8-yl; triphenylsilyl; triisopropylsilyl;        triphenylmethyl; tri(4-methylphenyl)methyl;        9-phenyl-fluorene-9-yl;        2-phenyl-1,1,1,3,3,3-hexafluoro-prop-2-yl;        2-methyl-1,1,1,3,3,3-hexafluoro-prop-2-yl; and t-butyl.    -   19. The method of embodiment 18, wherein:    -   R^(7a) is selected from the group consisting of pyrrol-1-yl;        2,5-dimethyl-pyrrol-1-yl; and    -   R^(8a) is phenyl which bears two substituents in the ortho        positions with respect to O, or which bears at least three        substituents, from which two substituents are in the ortho        positions with respect to O and one substituent is in the para        position with respect to O; or    -   R^(8a) is selected from the group consisting of optionally        substituted 8-(naphthalene-1-yl)-naphthalene-1-yl and optionally        substituted 8-phenlynaphthalene-1-yl.    -   20. The method of embodiment 16, wherein the metathesis catalyst        has a structure according to Formula 2a:

-   -   wherein:    -   R^(3a) is aryl, heteroaryl, alkyl, or cycloalkyl, each of which        is optionally substituted;    -   R^(7a) is pyrrolyl, imidazolyl, indolyl, pyrazolyl, azaindolyl,        or indazolyl, each of which is optionally substituted;    -   R^(8a) is optionally substituted aryl;    -   R^(5a) is a hydrogen atom, alkyl, or alkoxy;    -   R^(4b) is a hydrogen atom, —O—(C₁₋₆ alkyl), —CH₂—O—(C₁₋₆ alkyl),        heteroalkoxy, or —N(C₁₋₆ alkyl)₂; and    -   R^(4c) and R^(4d) are independently a hydrogen atom, C₁₋₆ alkyl,        C₁₋₆ alkoxy, a halogen atom, —NO₂, an amide, or a sulfonamide.    -   21. The method of embodiment 20, wherein:    -   R^(7a) is pyrrolyl, imidazolyl, pyrazolyl, azaindolyl, or        indazolyl, each of which is optionally substituted; and    -   R^(5a) is a hydrogen atom.    -   22. The method of embodiment 20, wherein R^(3a) is phenyl,        2,6-dichlorophenyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl,        2-trifluoromethylphenyl, pentafluorophenyl, tert-butyl, or        1-adamantyl.    -   23. The method of embodiment 20 or embodiment 22, wherein R^(8a)        is

-   -   24. The method of any one of embodiments 20-23, wherein R^(4b)        is methoxy, Roc is hydrogen, and R^(4d) is hydrogen.    -   25. The method of embodiment 15, wherein the metathesis catalyst        is selected from the group consisting of

-   -   26. The method of embodiment 25, wherein the metathesis catalyst        is

-   -   27. The method of embodiment 25, wherein the metathesis catalyst        is

-   -   28. The method of any one of embodiments 15-27, wherein the        catalyst is present in an amount less than 0.01 mol % with        respect to the olefin or to the metathesis reaction partner.    -   29. The method of any one of embodiments 1-10, wherein the        metathesis product comprises an E olefin.    -   30. The method of embodiment 29, wherein greater than about 85%        of the olefin is an E olefin.    -   31. The method of embodiment 29, wherein at least about 90% of        the olefin is an E olefin.    -   32. The method of any one of embodiments 29-31, wherein the        metathesis catalyst is an E-selective ruthenium catalyst.    -   33. The method of any one of embodiments 1-32, wherein the molar        ratio of the olefin to the metathesis reaction partner ranges        from about 1:1 to about 5:1.    -   34. The method of any one of embodiments 33, wherein the molar        ratio of the olefin to the metathesis reaction partner ranges        from about 2:1 to about 3:1    -   35. The method of any one of embodiments 1-34, wherein the        metathesis reaction partner is derived from a natural oil.    -   36. The method of embodiment 35, wherein the natural oil is        selected from the group consisting of canola oil, rapeseed oil,        coconut oil, corn oil, cottonseed oil, olive oil, palm oil,        peanut oil, safflower oil, sesame oil, soybean oil, sunflower        oil, linseed oil, palm kernel oil, tung oil, jatropha oil,        jojoba oil, mustard oil, pennycress oil, camelina oil, castor        oil, and combinations thereof    -   37. The method of embodiment 35 or 36, wherein the metathesis        reaction partner comprises one or more catalyst-poisoning        contaminants.    -   38. The method of embodiment 37, further comprising treating the        metathesis reaction partner with a metal alkyl compound under        conditions sufficient to reduce the concentration of at least        one of the catalyst-poisoning contaminants, wherein the treating        is conducted prior to contacting the olefin with the metathesis        reaction partner.    -   39. The method of embodiment 1, wherein    -   the olefin according to Formula I is a linear C₃-C₁₂ alpha        olefin,    -   the metathesis reaction partner according to Formula IIb is a        Δ⁹-unsaturated fatty acid alkyl ester,    -   the metathesis catalyst is a Z-selective metathesis catalyst,        and    -   the metathesis product according to Formula IIIb is a C₁₁-C₂₀        (Z)-9-unsaturated fatty acid alkyl ester.    -   40. The method of embodiment 39, wherein converting the        metathesis product to the fatty olefin derivative comprises        contacting the C₁₁-C₂₀ (Z)-9-unsaturated fatty acid alkyl ester        with a reducing agent under conditions sufficient to form a        C₁₁-C₂₀ (Z)-9-fatty alcohol.    -   41. The method of embodiment 40, wherein the reducing agent is        sodium bis(2-methoxyethoxy)aluminum hydride.    -   42. The method of embodiment 40, wherein converting the        metathesis product to the fatty olefin derivative further        comprises contacting the C₁₁-C₂₀ (Z)-9-fatty alcohol with an        acylating agent in the presence of a base under conditions        sufficient to form an acetate ester of the C₁₁-C₂₀ (Z)-9-fatty        alcohol.    -   43. The method of embodiment 42, wherein the acylating agent is        acetic anhydride.    -   44. The method of embodiment 40, wherein converting the        metathesis product to the fatty olefin derivative further        comprises oxidizing the C₁₁-C₂₀ (Z)-9-fatty alcohol to form a        C₁₁-C₂₀ (Z)-9-alkenal.    -   45. The method of embodiment 39, wherein converting the        metathesis product to the fatty olefin derivative comprises        contacting the C₁₁-C₂₀ (Z)-9-fatty acid alkyl ester with a        reducing agent under conditions sufficient to form a C₁₁-C₂₀        (Z)-9-alkenal.    -   46. The method of embodiment 45, wherein the reducing agent is        amine-modified sodium bis(2-methoxyethoxy)aluminumhydride.    -   47. The method of embodiment 1, wherein:    -   the fatty acid derivative is (Z)-tetradec-9-en-1-yl acetate;    -   the olefin according to Formula I is hex-1-ene,    -   the metathesis reaction partner according to Formula IIb is a        Δ⁹-unsaturated fatty acid alkyl ester,    -   the metathesis catalyst is a Z-selective metathesis catalyst,        and    -   the metathesis product according to Formula IIIb is an alkyl        ester of (Z)-9-tetradec-9-enoate; and    -   wherein converting the metathesis product to the fatty olefin        derivative comprises:    -   contacting the alkyl ester of (Z)-9-tetradec-9-enoate with a        reducing agent under conditions sufficient to form        (Z)-tetradec-9-en-1-ol, and    -   acylating the (Z)-tetradec-9-en-1-ol to form the        (Z)-tetradec-9-en-1-yl acetate.    -   48. The method of embodiment 47, wherein the metathesis reaction        partner according to Formula IIb is methyl 9-decenoate and the        metathesis product is methyl (Z)-tetradec-9-enoate.    -   49. The method of embodiment 47, wherein the reducing agent is        sodium bis(2-methoxyethoxy)aluminumhydride.    -   50. The method of embodiment 47, wherein acylating the        (Z)-tetradec-9-en-1-ol comprises contacting the        (Z)-tetradec-9-en-1-ol with an acylating agent in the presence        of a base under conditions sufficient to form        (Z)-tetradec-9-en-1-yl acetate.    -   51. The method of embodiment 50, wherein the acylating agent is        acetic anhydride.    -   52. The method of any one of embodiments 47-51, wherein the        metathesis reaction partner according to Formula IIb is methyl        9-decenoate and the metathesis product is methyl        (Z)-tetradec-9-enoate.    -   53. The method of embodiment 1, wherein:    -   the fatty acid derivative is (Z)-tetradec-9-enal,    -   the olefin according to Formula I is hex-1-ene,    -   the metathesis reaction partner according to Formula IIb is a        Δ⁹-unsaturated fatty acid alkyl ester,    -   the metathesis catalyst is a Z-selective metathesis catalyst,        and    -   the metathesis product according to Formula IIIb is an alkyl        ester of (Z)-9-tetradec-9-enoate; and    -   wherein converting the metathesis product to the fatty olefin        derivative comprises contacting the alkyl ester of        (Z)-9-tetradec-9-enoate with a reducing agent under conditions        sufficient to form the (Z)-tetradec-9-enal.    -   54. The method of embodiment 53, wherein the reducing agent is        amine-modified sodium bis(2-methoxyethoxy) aluminumhydride.    -   55. The method of embodiment 53 or embodiment 54, wherein the        Δ⁹-unsaturated fatty acid alkyl ester according to Formula IIg        is methyl 9-decenoate and the metathesis product is methyl        (Z)-tetradec-9-enoate.    -   56. The method of embodiment 1, wherein:    -   the fatty acid derivative is (Z)-tetradec-9-enal,    -   the olefin according to Formula I is hex-1-ene,    -   the metathesis reaction partner according to Formula IIb is a        Δ⁹-unsaturated fatty acid alkyl ester,    -   the metathesis catalyst is a Z-selective metathesis catalyst,        and    -   the metathesis product according to Formula IIIb is an alkyl        ester of (Z)-9-tetradec-9-enoate; and    -   wherein converting the metathesis product to the fatty olefin        derivative comprises    -   contacting the alkyl ester of (Z)-9-tetradec-9-enoate with a        reducing agent under conditions sufficient to form        (Z)-tetradec-9-en-1-ol, and    -   oxidizing the (Z)-tetradec-9-en-1-ol to form the        (Z)-tetradec-9-enal.    -   57. The method of embodiment 56, wherein the reducing agent is        sodium bis(2-methoxyethoxy)aluminumhydride.    -   58. The method of embodiment 56 or embodiment 57, wherein the        Δ⁹-unsaturated fatty acid alkyl ester according to Formula IIg        is methyl 9-decenoate and the metathesis product is methyl        (Z)-tetradec-9-enoate.    -   59. The method of any one of embodiments 39-58, wherein the        metathesis catalyst has a structure according to Formula 2a:

-   -   wherein:    -   M is Mo or W;    -   R^(3a) is aryl, heteroaryl, alkyl, or cycloalkyl, each of which        is optionally substituted;    -   R^(7a) is pyrrolyl, imidazolyl, indolyl, pyrazolyl, azaindolyl,        or indazolyl, each of which is optionally substituted;    -   R^(8a) is optionally substituted aryl;    -   R^(5a) is a hydrogen atom, alkyl, or alkoxy;    -   R^(4b) is a hydrogen atom, —O—(C₁₋₆ alkyl), —CH₂—O—(C₁₋₆ alkyl),        heteroalkoxy, or —N(C₁₋₆ alkyl)₂; and    -   R^(4c) and R^(4d) are independently a hydrogen atom, C₁₋₆ alkyl,        C₁₋₆ alkoxy, a halogen atom, —NO₂, an amide, or a sulfonamide.    -   60. The method of embodiment 59, wherein the metathesis catalyst        is selected from the group consisting of:

-   -   61. A fatty olefin derivative synthesized according to the        method of any one of embodiments 1-60.    -   62. The fatty olefin derivative of embodiment 61, which is an        insect pheromone.    -   63. A method for synthesizing a fatty olefin derivative        according to Formula VIb:

-   -   the method comprising:    -   i) reducing an alkyl ester according to Formula IIb

-   -   to form an alkenol according to Formula VIII

-   -   ii) acylating the alkenol to form an acylated alkenol according        to Formula IX

and

-   -   iii) contacting the acylated alkenol with an olefin according to        Formula I

-   -   in the presence of a metathesis catalyst under conditions        sufficient to form the fatty olefin derivative; wherein:    -   R¹ is selected from the group consisting of H, C₁₋₁₈ alkyl, and        C₂₋₁₈ alkenyl;    -   R^(2b) is C₁₋₈ alkyl,    -   R^(2c) is C₁₋₆ acyl,    -   subscript y is an integer ranging from 0 to 17;    -   subscript z is an integer ranging from 0 to 17; and    -   the metathesis catalyst is a tungsten catalyst or a molybdenum        catalyst.    -   64. The method of embodiment 63, wherein R¹ is H, R^(2b) is        methyl, R^(2c) is acetyl, subscript y is 7, and subscript z is        3.    -   65. The method of embodiment 63 or embodiment 64, wherein the        metathesis product comprises an E olefin.    -   66. The method of embodiment 63 or embodiment 64, wherein the        metathesis product comprises a Z olefin.    -   67. The method of embodiment 66, wherein the metathesis catalyst        is a Z-selective molybdenum catalyst or a Z-selective tungsten        catalyst.    -   68. The method of embodiment 67, wherein the metathesis catalyst        has a structure according to Formula 2:

-   -   wherein:    -   M is Mo or W;    -   R^(3a) is selected from the group consisting of aryl,        heteroaryl, alkyl, heteroalkyl, cycloalkyl, and        heterocycloalkyl, each of which is optionally substituted;    -   R^(4a) and R^(5a) are independently selected from the group        consisting of hydrogen, optionally substituted alkyl, optionally        substituted alkenyl, optionally substituted heteroalkyl,        optionally substituted heteroalkenyl, optionally substituted        aryl, and optionally substituted heteroaryl;    -   R^(7a) is selected from the group consisting of alkyl, alkoxy,        heteroalkyl, aryl, aryloxy, heteroaryl, silylalkyl, and        silyloxy, each of which is optionally substituted; and    -   R^(6a) is R^(8a)—X—, wherein    -   X is O or S and R^(8a) is optionally substituted aryl; or    -   X is O and R^(8a) is SiR^(9a)R^(10a)R^(11a) or        CR^(12a)R^(13a)R^(14a), wherein R^(9a), R^(10a), R^(11a),        R^(12a), R^(13a), and R^(14a) are independently selected from        the group consisting of optionally substituted alkyl and        optionally substituted phenyl; or    -   R^(6a) and R^(7a) are linked together and are bonded to M via        oxygen.    -   69. The method of embodiment 68, wherein the metathesis catalyst        has a structure according to Formula 2a:

-   -   wherein:    -   R^(3a) is aryl, heteroaryl, alkyl, or cycloalkyl, each of which        is optionally substituted;    -   R^(7a) is pyrrolyl, imidazolyl, indolyl, pyrazolyl, azaindolyl,        or indazolyl, each of which is optionally substituted;    -   R^(8a) is optionally substituted aryl;    -   R^(5a) is a hydrogen atom, alkyl, or alkoxy;    -   R^(4b) is a hydrogen atom, —O—(C₁₋₆ alkyl), —CH₂—O—(C₁₋₆ alkyl),        heteroalkoxy, or —N(C₁₋₆ alkyl)₂; and    -   R^(4c) and R^(4d) are independently a hydrogen atom, C₁₋₆ alkyl,        C₁₋₆ alkoxy, a halogen atom, —NO₂, an amide, or a sulfonamide.    -   70. The method of embodiment 68 or embodiment 69, wherein the        metathesis catalyst is selected from the group consisting of:

Although the foregoing has been described in some detail by way ofillustration and example for purposes of clarity and understanding, oneof skill in the art will appreciate that certain changes andmodifications can be practiced within the scope of the appended claims.All publications, patents, patent applications, and sequence accessionnumbers cited herein are hereby incorporated by reference in theirentirety for all purposes.

What is claimed is:
 1. A method for synthesizing a compound according toFormula VIb:

the method comprising: acylating an alkenol according to Formula VIII

to form an acylated alkenol according to Formula IX

 and contacting the acylated alkenol with an olefin according to FormulaI

in the presence of a metathesis catalyst having a structure according toFormula 2a

thereby forming the compound of Formula VIb; wherein: R¹ is selectedfrom the group consisting of H, C₁₋₁₈ alkyl, and C₂₋₁₈ alkenyl; R^(2c)is C₁₋₆ acyl, subscript y is an integer ranging from 0 to 17; subscriptz is an integer ranging from 0 to 17; M is Mo or W; R^(3a) is aryl,heteroaryl, alkyl, or cycloalkyl, each of which is optionallysubstituted; R^(7a) is pyrrolyl, imidazolyl, indolyl, pyrazolyl,azaindolyl, or indazolyl, each of which is optionally substituted;R^(8a) is optionally substituted aryl; R^(5a) is a hydrogen atom, alkyl,or alkoxy; R^(4b) is a hydrogen atom, —O—(C₁₋₆ alkyl), —CH₂—O—(C₁₋₆alkyl), heteroalkoxy, or —N(C₁₋₆ alkyl)₂; and R^(4c) and R^(4d) areindependently a hydrogen atom, C₁₋₆ alkyl, C₁₋₆ alkoxy, a halogen atom,—NO₂, an amide, or a sulfonamide.
 2. The method of claim 1, wherein thealkenol according to Formula VIII is formed by reducing an alkyl esteraccording to Formula IIb:

wherein R^(2b) is C₁₋₈ alkyl.
 3. The method of claim 1, wherein thecompound of Formula VIb is selected from (Z)-7-dodecenyl acetate;(E)-7-dodecenal; (Z)-7-decenyl acetate; (Z)-7-hexadecenal;(Z)-7-hexadecenyl acetate; (Z)-7-tetradecenal; (Z)-7-tetradecenylacetate; (Z)-7-undecenyl acetate; (Z)-10-dodecenyl acetate;(Z)-10-hexadecenyl acetate; (Z)-10-pentadecenal; (Z)-10-pentadecenylacetate; (Z)-10-tetradecenyl acetate; (Z)-10-tridecenyl acetate;(Z)-9-dodecenal; (Z)-9-dodecenyl acetate; (Z)-9-hexadecenal;(Z)-9-hexadecenyl acetate; (Z)-9-pentadecenyl acetate;(Z)-9-tetradecenal; (Z)-9-tetradecenyl acetate; (Z)-9-tetradecenylformate; (Z)-9-tetradecenyl nitrate; (Z)-9-tridecenyl acetate;(Z)-9-undecenyl acetate; (Z)-11-hexadecen-1-ol; (Z)-11-hexadecenal;(Z)-11-hexadecenyl acetate; (Z)-11-tetraceden-1-ol; (Z)-11-tetracedenylacetate; (Z)-13-octadecen-1-ol; and (Z)-13-octadecenal.
 4. The method ofclaim 1, wherein: R^(7a) is pyrrolyl, imidazolyl, pyrazolyl, azaindolyl,or indazolyl, each of which is optionally substituted; and R^(5a) is ahydrogen atom.
 5. The method of claim 1, wherein R^(3a) is phenyl,2,6-dichlorophenyl, 2,6-dimethylphenyl, 2,6-diisopropylphenyl,2-trifluoromethylphenyl, pentafluorophenyl, tert-butyl, or 1-adamantyl.6. The method of claim 5, wherein R^(8a) is:


7. The method of claim 1, wherein R^(4b) is methoxy, R^(4c) is hydrogen,and R^(4d) is hydrogen.
 8. The method of claim 1, wherein the metathesiscatalyst is:


9. The method of claim 1, wherein the catalyst is present in an amountless than 0.01 mol % with respect to the olefin or to the metathesisreaction partner.
 10. The method of claim 3, wherein the compound ofFormula VIb comprises at least 80% Z olefin.
 11. The method claim 1,wherein acylating the alkenol according to Formula VIII is conductedwith an acylating agent selected from the group consisting of aceticanhydride and acetyl chloride.
 12. The method claim 11, wherein 1-5molar equivalents of the acylating agent with respect to the alkenolaccording to Formula VIII is used.